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. 2016 May 2;14(5):87. doi: 10.3390/md14050087

Bioprospecting Sponge-Associated Microbes for Antimicrobial Compounds

Anak Agung Gede Indraningrat 1,2, Hauke Smidt 1, Detmer Sipkema 1,*
Editor: Kirsten Benkendorff
PMCID: PMC4882561  PMID: 27144573

Abstract

Sponges are the most prolific marine organisms with respect to their arsenal of bioactive compounds including antimicrobials. However, the majority of these substances are probably not produced by the sponge itself, but rather by bacteria or fungi that are associated with their host. This review for the first time provides a comprehensive overview of antimicrobial compounds that are known to be produced by sponge-associated microbes. We discuss the current state-of-the-art by grouping the bioactive compounds produced by sponge-associated microorganisms in four categories: antiviral, antibacterial, antifungal and antiprotozoal compounds. Based on in vitro activity tests, identified targets of potent antimicrobial substances derived from sponge-associated microbes include: human immunodeficiency virus 1 (HIV-1) (2-undecyl-4-quinolone, sorbicillactone A and chartarutine B); influenza A (H1N1) virus (truncateol M); nosocomial Gram positive bacteria (thiopeptide YM-266183, YM-266184, mayamycin and kocurin); Escherichia coli (sydonic acid), Chlamydia trachomatis (naphthacene glycoside SF2446A2); Plasmodium spp. (manzamine A and quinolone 1); Leishmania donovani (manzamine A and valinomycin); Trypanosoma brucei (valinomycin and staurosporine); Candida albicans and dermatophytic fungi (saadamycin, 5,7-dimethoxy-4-p-methoxylphenylcoumarin and YM-202204). Thirty-five bacterial and 12 fungal genera associated with sponges that produce antimicrobials were identified, with Streptomyces, Pseudovibrio, Bacillus, Aspergillus and Penicillium as the prominent producers of antimicrobial compounds. Furthemore culture-independent approaches to more comprehensively exploit the genetic richness of antimicrobial compound-producing pathways from sponge-associated bacteria are addressed.

Keywords: antimicrobial compounds, sponges, sponge-associated microbes

1. Introduction

Antimicrobial resistance (AMR) is an emerging global threat, decreasing the possibilities for prevention and treatment of infectious diseases caused by viruses, bacteria, parasites and fungi [1,2]. A global surveillance report by the World Health Organization (WHO) [2] indicated an increase of morbidity and mortality of infectious diseases due to AMR, which could lead to a world-wide economic loss of up to 100 trillion US dollars (USD) in 2050 as the result of a 2%–3% reduction in the gross domestic product (GDP) [1]. A conservative estimation is that AMR now annually attributes to 700,000 deaths globally, with a potential leap to 10 million in 2050 [1]. AMR is a response of microorganisms against antimicrobial compounds, which can arise via several mechanisms such as chromosomal mutations [1], binding site modifications [2] or horizontal transfer of genes conferring resistance [3]. For several pathogenic bacteria such as Staphylococcus aureus [4], Pseudomonas aeruginosa [1,5], and Mycobacterium tuberculosis [6], the emergence of multi drug resistant (MDR) strains has been reported, which make infections with these strains increasingly difficult to treat with currently available antibiotics [3].

In the context of the arms race between humans and infectious agents, the discovery and development of new types of antimicrobial compounds with pronounced bioactivity and clinical significance are urgent [4,5]. The efforts to modify existing drugs are often not effective to overcome the mutation rate of pathogens and do not lead to the introduction of new classes of antimicrobial compounds [6]. The terrestrial environment has been the main focus of microbial-derived drug discovery since the first report on Penicillin in 1929 [7], followed by the booming of new classes of antibiotics in 1960s [8]. Although novel antimicrobials are still being discovered from the soil niche, e.g., turbomycin A and B [9] and teixobactin [10], there are issues with de-replication, which significantly reduces the discovery rate of new compounds from heavily screened environments [11].

In comparison with soils, the marine environment has been largely neglected for discovery of antibiotics until recently, mainly because of accessibility issues, but yet hold a huge biodiversity and potential novelty of antimicrobial compounds [12]. Of many marine organisms, sponges (phylum Porifera) are considered as the most prolific source of therapeutic compounds as these animals harbour a large variety of secondary metabolites, many of which are beneficial for human health purposes [13,14,15,16,17]. The “Supply Issue” is the main obstacle to exploit the biological activity of sponges’ metabolites since a large quantity of biomaterial is required for experimental purposes [13]. Interestingly, in recent years an increasing number of studies highlighted that many active substances from sponges are of bacterial origin due to similarity to chemical structures found in terrestrial microorganisms [13,14,15]. Furthermore, several studies have reported a wide diversity of antimicrobial activities from sponge-associated microbes, which make these microbial communities a valuable source for novel antimicrobials [14,16,17,18,19,20].

This review highlights the current knowledge of antimicrobial compounds produced by sponge-associated microbes. Our definition of “antimicrobial” is not limited to antibacterial agents, but also includes compounds active against viruses, fungi and infectious protozoa. For each of the four biological activities, a few substances are highlighted because of their high activity, along with the most complete overview to date of other known compounds with antimicrobial activity from sponge-associated microorganisms. To compare different bioactive compounds and crude extracts, inhibitory concentrations of substances reviewed have been as much as possible expressed in the same unit (µg/mL). Original articles use minimum inhibitory concentrations (MIC), half maximum inhibitory concentrations (IC50) and the concentration of a drug that give the half-maximal response (EC50). As they are not easily converted, we sticked to the original measures.

Moreover, we analyzed the distribution of bacterial and fungal genera associated with sponges that have been reported to produce antimicrobial compounds to identify the most prolific genera. In addition, the potential for application of metagenomics to complement culture-dependent antimicrobial screening strategies is also discussed.

2. Antiviral Compounds

New antiviral compounds are needed due to the increased occurrence of diseases caused by viral infections and because of antiviral escape strategies [21]. Marine organisms, and sponges in particular, have been shown to be a valuable source for antivirals. For example, the discovery of the nucleosides spongothymidine and spongouridine from the sponge Tethya crypta was the basis for the compound Ara-A (vidarabine) that is active against the herpes simplex virus [21,22,23,24].

Screening of sponge-associated microbes yielded several prospective anti-HIV-1 (human immunodeficiency virus-1) compounds (Table 1 and Figure 1). Bultel-Poncé et al. [25] isolated Pseudomonas sp. 1531-E7 from the marine sponge Homophymia sp. resulting in the discovery of the antiviral compound 2-undecyl-4-quinolone (1) (Figure 1). The compound had an IC50 concentration as low as 10−3 µg/mL in vitro against HIV-1. Bringmann et al. [26] elucidated the chemical structure of sorbicillactone A (2) which was isolated from Penicillium chrysogenum, a fungus associated with the sponge Ircinia fasciculata. Sorbicillactone A displayed cytoprotective effects on HIV-1-infected cells of the human cell line H9 at concentrations of 0.1–1 µg/mL. In addition, in vitro testing using H9 cells indicated that sorbicillactone A reduced the appearance of the HIV-1 protein up to 70% at a concentration of 0.3 μg/mL [26]. The sponge-associated fungus Stachybotrys chartarum MXH-X73 produces the compound stachybotrin D (3), which exhibited anti-HIV-1 activity by targeting reverse transcriptase [27]. At EC50 concentrations from 2.73 µg/mL to 10.51 µg/mL, stachybotrin D was active not only against the wild type HIV-1 but also against several non-nucleoside reverse transcriptase inhibitor (NNRTI) resistant HIV-1 strains. Li et al. [28] reported identification of three other anti-HIV-1 compounds from Stachybotrys chartarum: chartarutine B, G, and H. Of these three chartarutine compounds, chartarutine B (4) showed the lowest concentration that resulted in 50% inhibition of HIV-1 (IC50 of 1.81 µg/mL), followed by chartarutine G (IC50 of 2.05 µg/mL) and chartarutine H (IC50 of 2.05 µg/mL), respectively.

Table 1.

Bioactive compounds with antiviral activity from sponge-associated microbes.

Sponge Origin (Depth) Microorganism Phylum Compound Property Target Reference
Homophymia sp. Touho, New Caledonia (ND) Pseudomonas sp. 1531-E7 Proteobacteria 2-undecyl-4-quinolone IC50 (10−3 µg/mL) HIV-1 [25]
Ircinia fasciculata Bight of Fetovaia, Italy (17.5 m) Penicillium chrysogenum Ascomycota Sorbicillactone A Reducing protein expression and activity of reverse transcriptase (0.3–1 µg/mL) HIV-1 [26]
Xestospongia testudinaria Paracel Islands (ND) Stachybotrys chartarum MXH-X73 Ascomycota Stachybotrin D EC50 (3.71 µg/mL) HIV-1 [27]
Xestospongia testudinaria Paracel Islands (ND) Stachybotrys chartarum MXH-X73 Ascomycota Stachybotrin D EC50 (3.09 µg/mL) Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistant
HIV-1 strain 1RT-K103N
[27]
Xestospongia testudinaria Paracel Islands (ND) Stachybotrys chartarum MXH-X73 Ascomycota Stachybotrin D EC50 (10.51 µg/mL) NNRTI resistant
HIV-1RT-L100I, K103N
[27]
Xestospongia testudinaria Paracel Islands (ND) Stachybotrys chartarum MXH-X73 Ascomycota Stachybotrin D EC50 (5.87 µg/mL) NNRTI resistant
HIV-1RT-K103N, V108I
[27]
Xestospongia testudinaria Paracel Islands (ND) Stachybotrys chartarum MXH-X73 Ascomycota Stachybotrin D EC50 (6.27 µg/mL) NNRTI resistant
HIV-1RT-K103N, G190A
[27]
Xestospongia testudinaria Paracel Islands (ND) Stachybotrys chartarum MXH-X73 Ascomycota Stachybotrin D EC50 (2.73 µg/mL) NNRTI resistant
HIV-1RT-K103N, P225H
[27]
Niphates sp. Beibuwan Bay, China (10 m) Stachybotrys chartarum Ascomycota Chartarutine B IC50 (1.81 µg/mL) HIV-1 [28]
Niphates sp. Beibuwan Bay, China (10 m) Stachybotrys chartarum Ascomycota Chartarutine G IC50 (2.05 µg/mL) HIV-1 [28]
Niphates sp. Beibuwan Bay, China (10 m) Stachybotrys chartarum Ascomycota Chartarutine H IC50 (2.05 µg/mL) HIV-1 [28]
Amphimedon sp. Yongxin island, China (10 m) Truncatella angustata Ascomycota Truncateol M IC50 (2.91 µg/mL) H1N1 [29]
Callyspongia sp. Sanya, China (ND) Epicoccum sp. JJY40 Ascomycota Pyronepolyene C-glucoside iso-D8646-2-6 IC50 (56.06 µg/mL) H1N1 [33]
Callyspongia sp. Sanya, China (ND) Epicoccum sp. JJY40 Ascomycota Pyronepolyene C-glucoside, 8646-2-6 IC50 (62.07 µg/mL) H1N1 [33]
Unidentified Naozhou Sea, China (ND) Aspergillus terreus MXH-23 Ascomycota Butyrolactone III Percentage of inhibition (53.9% ± 0.53% at 50 µg/L) H1N1 [34]
Unidentified Naozhou Sea, China (ND) Aspergillus terreus MXH-23 Ascomycota 5-[(3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-yl)-methyl]-3-hydroxy-4-(4-hydroxyphenyl)-2(5H)-furanone Percentage of inhibition (57.8% ± 1.99% at 50 µg/L) H1N1 [34]
Unidentified Paracel Islands (ND) Aspergillus sydowii ZSDS1-F6 Ascomycota (Z)-5-(Hydroxymethyl)-2-(60)-methylhept-20-en-20-yl)-phenol IC50 (14.30 µg/mL) H3N2 [35]
Unidentified Paracel Islands (ND) Aspergillus sydowii ZSDS1-F6 Ascomycota Diorcinol IC50 (15.31 µg/mL) H3N2 [35]
Unidentified Paracel slands (ND) Aspergillus sydowii ZSDS1-F6 Ascomycota Cordyol C IC50 (19.33 µg/mL) H3N2 [35]
Unidentified Paracel Islands (ND) Stachybotrys sp. HH1 ZSDS1F1-2 Ascomycota Stachybogrisephenone B IC50 (10.2 µg/mL) Enterovirus 71 (EV71) [36]
Unidentified Paracel Islands (ND) Stachybotrys sp. HH1 ZSDS1F1-2 Ascomycota Grisephenone A IC50 (16.94 µg/mL Enterovirus 71 (EV71) [36]
Unidentified Paracel Islands (ND) Stachybotrys sp. HH1 ZSDS1F1-2 Ascomycota 3,6,8-Trihydroxy-1-methylxanthone IC50 (10.4 µg/mL) Enterovirus 71 (EV71) [36]
Petromica citrina Saco do Poço, Brazil (5–15 m) Bacillus sp. B555 Firmicutes Unidentified IC50 (27.35 μg/mL)
EC50 (>500 μg/mL)
Bovine viral diarrhea virus [37]
Petromica citrina Saco do Poço, Brazil (5–15 m) Bacillus sp. B584 Firmcutes Unidentified IC50 (10.24 μg/mL)
EC50 (277 μg/mL)
Bovine viral diarrhea virus [37]
Petromica citrina Saco do Poço, Brazil (5–15 m) Bacillus sp. B616 Firmicutes Unidentified IC50 (47 μg/mL)
EC50 (1500 μg/mL)
Bovine viral diarrhea virus [37]

Table 1 is organised according to the target virusses. IC50: half maximum inhibitory concentration; EC50: the concentration of a drug that give the half-maximal response; ND: not determined; HIV: human immunodeficiency virus; H1N1 and H3N2 are influenza A virus subtypes.

Figure 1.

Figure 1

Chemical structures of the antiviral compounds 2-undecyl-4-quinolone (1), sorbicillactone A (2), stachybotrin D (3), chartarutine B (4), and truncateol M (5).

Sponge-associated microbes have also been found to produce anti-influenza compounds (Table 1). Zhao et al. [29] elucidated 14 new isoprenylated cyclohexanols coined as truncateols A-N from the sponge-associated fungus Truncatella angustata, and these compounds were tested in vitro against the influenza A (H1N1) virus. Truncateols C, E and M displayed bioactivity against H1N1, with truncateol M (5) being the most potent inhibitor, as shown by its IC50 value of 2.91 µg/mL. This inhibitory concentration was almost six fold lower than that of the positive control oseltamivir at 14.52 µg/mL. Truncateol M was predicted to be active at the late stage of the virus infection, likely during the assembly or release step of the virion [29] due to resemblance of the inhibition patterns observed for neuraminidase-inhibitor drugs, e.g., zanamivir and oseltamivir [30]. In addition, the presence of a chlorine atom in the chemical structure of trucanteol M is of particular interest since halogenation often enhances bioactivity of a given compound [31,32].

3. Antibacterial Compounds

The screening procedure for antibacterial activity often includes both Gram positive and Gram negative target strains, including, e.g., Staphylococcus spp., Streptococcus spp., Bacillus spp., Clostridium spp., Escherichia spp., and Pseudomonas spp. From a medical point of view, these genera receive attention because they are well represented among the causative agents for human infectious diseases, such as pneumonia, urinary tract and blood stream infections [38,39]. Microbial isolates from marine sponges have been shown to exhibit bioactivity against a wide spectrum of pathogenic bacteria (Table 2). The novel thiopeptide antibiotics YM-266183 (6) and YM-266184 (7) (Figure 2), which were isolated from the sponge-associated bacterium Bacillus cereus QN03323, showed antibacterial activity against nosocomial infectious Gram positive bacteria in vitro [40,41]. Both YM-266183 and YM-266184 effectively inhibited Staphylococcus aureus and vancomycin-resistant Enterococcus faecium as indicated by minimal inhibition concentration (MIC) values as low as 0.025 µg/mL. In addition, compound YM-266184 was found particularly active against methicillin resistant Staphylococcus aureus (MRSA) with a MIC of 0.39 µg/mL. Compound YM-266183 also inhibited MRSA but required a two-fold higher concentration of the pure compound. Bioactivity of these thiopeptides was also observed against Streptococcus epidermidis and Enterococcus spp. (Table 2). The compound kocurin (8) was identified from three sponge-associated actinobacteria: Kocuria marina F-276,310, Kocuria palustris F-276,345, and Micrococcus yunnanensis F-256,446 [42,43]. Kocurin is a new member of the thiazolyl peptide family and exhibited anti-MRSA activity with an MIC of 0.25 µg/mL, which to date is the most potent anti-MRSA compound reported from sponge-associated microbes. Scheenemaan et al. [44] isolated Streptomyces sp. HB202 from the sponge Haliclona simulans, which lead to discovery of the polyketide mayamycin. In vitro assays with mayamycin (9) showed bioactivity against S. aureus and MRSA with IC50 values of 1.16 µg/mL and 0.58 µg/mL respectively, along with an IC50 of 0.14 µg/mL against Staphylococcus epidermidis [45].

Table 2.

Bioactive compounds with antibacterial activity from sponge-associated microbes.

Sponge Origin (Depth) Microorganism Phylum Compound Property Target References
Halichondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266183 MIC (0.025 µg/mL) Staphylococcus aureus [40,41]
Halichondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266184 MIC (0.025 µg/mL) S. aureus [40,41]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Mayamycin IC50 (1.16 µg/mL) S. aureus [45]
Spheciospongia vagabunda Red Sea (ND) Micrococcus sp. EG45 Actinobacteria Microluside A MIC (12.42 µg/mL) S. aureus NCTC 8325 [54]
Isodictya setifera Ross island, Antartica (30–40 m) Pseudomonas aeruginosa Proteobacteria Phenazine-1-carboxylic acid MIC (>4.99 µg/mL) S. aureus [55]
Isodictya setifera Ross island, Antartica (30–40 m) Pseudomonas aeruginosa Proteobacteria Phenazine-1-carboxamide MIC (>4.99 µg/mL) S. aureus [55]
Hymeniacidon perleve Bohai Sea, China (ND) Aspergillus versicolor MF359 Ascomycota 5-Methoxydihydrosterigmatocystin MIC (12.5 µg/mL) S. aureus [56]
Melophus sp. Lau group, Fiji islands (10 m) Penicillium sp. FF001 Ascomycota Citrinin MIC (1.95 µg/mL) S. aureus [57]
Petrosia sp. Jeju island, Korea (20 m) Aspergillus versicolor Ascomycota Averantin MIC (3.13 µg/mL) S. aureus SG511 [58]
Petrosia sp. Jeju island, Korea (20 m) Aspergillus versicolor Ascomycota Nidurufin MIC (6.25 µg/mL) S. aureus SG511 [58]
Petrosia sp. Jeju island, Korea (20 m) Aspergillus versicolor Ascomycota Averantin and nidurufin MIC (3.13 µg/mL) S. aureus 285 [58]
Petrosia sp. Jeju island, Korea (20 m) Aspergillus versicolor Ascomycota Averantin MIC (1.56 µg/mL) S. aureus 503 [58]
Petrosia sp. Jeju island, Korea (20 m) Aspergillus versicolor Ascomycota Nidurufin MIC (3.13 µg/mL) S aureus 503 [58]
Hymeniacidon perleve Nanji island, China (ND) Pseudoalteromonas piscicida NJ6-3-1 Ascomycota Norharman (beta-carboline alkaloid) MIC (50 µg/mL) S. aureus [59]
Halichondria panicea Bogil island, Korea (ND) Exophiala sp. Ascomycota Chlorohydroaspyrones A MIC (62.5 µg/mL) S. aureus [60]
Halichondria panicea Bogil island, Korea (ND) Exophiala sp. Ascomycota Chlorohydroaspyrones B MIC (62.5 µg/mL) S. aureus [60]
Axinella sp. South China Sea, China (ND) Eupenicillium sp. Ascomycota αβ-Dehydrocurvularin MIC (375 µg/mL) S. aureus [61]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40, H41 and Pseudomonas aeruginosa H51 Proteobacteria Diketopiperazine MIC (512 µg/mL) S. aureus [62]
Spongia officinalis Southeast Coast India (10–15 m) Streptomyces sp. MAPS15 Actinobacteria 2-pyrrolidone MIC (500 µg/mL) S. aureus PC6 [63]
Dysidea herbacea Koror, Republic Palau (1 m) Oscillatoria spongeliae Cyanobacteria 2-(2′,4′-dibromophenyl)-4,6-dibromophenol ND S. aureus [64]
Hyrtios altum Aragusuku island, Japan (ND) Vibrio sp. Proteobacteria Trisindoline DOI (10 mm) S. aureus [65]
Xestospongia testudinaria Bidong Island, Malaysia (ND) Serratia marcescens IBRL USM 84 Proteobacteria Prodigiosin DOI (≤9 mm) S. aureus [66]
unidentified South China Sea (10 m) Nocardiopsis sp. 13-33-15 and 13-12-13 Actinobacteria 1,6-Dihydroxyphenazine DOI (25 ± 0.6 mm) S. aureus SJ51 [67]
1,6-Dimethoxyphenazine DOI (21 ± 0.1 mm) S. aureus SJ51
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A184 Firmicutes Surfactin Iturin Fengycin ND S. aureus [68]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A190 Firmicutes Surfactin ND S. aureus [68]
Halichondria sp. West Coast of India (10 m) Bacillus licheniformis SAB1 Firmicutes Indole DOI (7–10 mm) S. aureus [69]
3-Phenylpropionic DOI (4–6 mm) S. aureus
Niphates olemda Bali Bata National Park, Indonesia (ND) Curvularia lunata Ascomycota 1,3,8-Trihydroxy-6-methoxyanthraquinone (lunatin) DOI (10 mm) S. aureus [70]
Bisanthraquinone cytoskyrin A
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Bacillus subtilis MMA7 Firmicutes Subtilomycin ND S. aureus [71]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W64, W69, W89, W74 Proteobacteria Tropodithietic acid DOI (≥2 mm) S. aureus [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. JIC17, W10, W71, W74, W78, W96, WM33, WC15, WC30, HMMA3 Actinobacteria Unidentified DOI (≥1 mm) S. aureus [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. JIC5, JIC6, W62, W63, W65, W99, WC43, W85, W94, WM31, WM34, WM40, WC13, WC21, WC22, WC32, WC41, HC6, Proteobacteria Unidentified DOI (≥4 mm) S. aureus [72]
Dendrilla nigra Vizhinjam coast, India (10–15 m) Streptomyces sp. MSI051 Ascomycota Unidentified MIC (68 ± 2.8 µg protein/mL) S. aureus [73]
Hymeniacidon perleve Nanji Island, China (ND) Pseudomonas sp. NJ6-3-1 Proteobacteria Unidentified DOI (3–5 mm) S. aureus [74]
Callyspongia spp Kovalam Coast, India (5–10 m) Aspergillus flavus GU815344 Proteobacteria Unidentified DOI (27 mm) S. aureus [75]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (20 mm) S. aureus [76]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (23 mm) S. aureus [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Firmicutes Unidentified DOI (20 mm) S. aureus [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (30 mm) S. aureus [77]
Dragmacidon reticulatus Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Dr31 Actinobacteria Unidentified DOI (19 mm) S. aureus [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (40 mm) S. aureus [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (40 mm) S. aureus [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (28 mm) S. aureus [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (27 mm) S. aureus [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (20 mm) S. aureus [77]
Axinella dissimilis Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio Ad30 Proteobacteria Unidentified ND S. aureus [78]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. M102, M403, M412, M413, M414, SW10, SW15 and SW17 Actinobacteria Unidentified DOI (>5 mm) S. aureus [79]
Pseudoceratina clavata Heron Island, Australia (14 m) Salinispora sp. SW02 Actinobacteria Unidentified DOI (<5 mm) S. aureus [79]
Dendrilla nigra Southeast coast of India (ND) Streptomyces sp. BTL7 Actinobacteria Unidentified DOI (16 mm) S. aureus [80]
Mycale sp. Gulei Port, Fujian, China (ND) Bacillus sp. HNS004, HNS010 Firmicutes Unidentified DOI (15–30 mm) S. aureus [81]
Mycale sp. Gulei Port, Fujian, China (ND) Vibrio sp. HNS022, HNS029 Proteobacteria Unidentified DOI (15–30 mm) S. aureus [81]
Mycale sp. Gulei Port, Fujian, China (ND) Streptomyces sp. HNS054 Actinobacteria Unidentified DOI (15–30 mm) S. aureus [81]
Mycale sp. Gulei Port, Fujian, China (ND) Bacillus sp. HNS005 Firmicutes Unidentified DOI (10–15 mm) S. aureus [81]
Mycale sp. Gulei Port, Fujian, China (ND) Cobetia sp. HNS027; Streptomyces sp. HNS047, HNS056; Nocardiopsis sp. HNS048, HNS051, HNS055; Nocardia sp. HNS052 Actinobacteria Unidentified DOI (10–15 mm) S. aureus [81]
Mycale sp. Gulei Port, Fujian, China (ND) Bacillus sp. HNS015 Firmicutes Unidentified DOI (8–10 mm) S. aureus [81]
Mycale sp. Gulei Port, Fujian, China (ND) Pseudomonas sp. HNS021 Proteobacteria Unidentified DOI (8–10 mm) S. aureus [81]
Mycale sp. Gulei Port, Fujian, China (ND) Cobetia sp. HNS023; Vibrio sp. HNS038; Labrenzia sp. HNS063; Streptomyces sp. HNS049; Nocardiopsis sp. HNS058 Actinobacteria Unidentified DOI (8–10 mm) S. aureus [81]
unidentified Rovinj, Croatia (3–20 m) Streptomyces sp. RV15 Actinobacteria Unidentified DOI (17 mm) S. aureus [82]
unidentified Rovinj, Croatia (3–20 m) Dietzia sp. EG67 Actinobacteria Unidentified DOI (13 mm) S. aureus [82]
unidentified Rovinj, Croatia (3–20 m) Microbacterium sp. EG69 Actinobacteria Unidentified DOI (13 mm) S. aureus [82]
unidentified Rovinj, Croatia (3–20 m) Micromonospora sp. RV115 Actinobacteria Unidentified DOI (12 mm) S. aureus [82]
unidentified Rovinj, Croatia (3–20 m) Rhodococcus sp. EG33 Actinobacteria Unidentified DOI (12 mm) S. aureus [82]
unidentified Rovinj, Croatia (3–20 m) Rubrobacter sp. RV113 Actinobacteria Unidentified DOI (9 mm) S. aureus [82]
Suberites carnosus Lough Hyne, Co. Cork, Ireland (15 m) Arthrobacter sp. W13C11 Actinobacteria Unidentified ND S. aureus [83]
Suberites carnosus Lough Hyne, Co. Cork, Ireland (15 m) Pseudovibrio sp. W13S4, W13S21, W13S23, W13S26, W13S31 Proteobacteria Unidentified ND S. aureus [83]
Aplysina aerophoba and Aplysina cavernicola Marseille and Banyuls sur Mer, France (ND) Bacillus SB8, SB17, Enterococcus SB91 Firmicutes Unidentified DOI (12–16 mm) S. aureus [84]
Aplysina aerophoba and Aplysina cavernicola Marseille and Banyuls sur Mer, France (ND) Arthrobacter SB95 Actinobacteria Unidentified DOI (12–16 mm) S. aureus [84]
Aplysina aerophoba and Aplysina cavernicola Marseille and Banyuls sur Mer, France (ND) unidentified low G + C Gram positive SB122 and SB144 Unidentified Unidentified DOI (12–16 mm) S. aureus [84]
Aplysina aerophoba and Aplysina cavernicola Marseille and Banyuls sur Mer, France (ND) α-Proteobacteria SB6, SB55, SB63, SB89, SB156, SB197, SB202, SB207, SB214 Proteobacteria Unidentified DOI (12–16 mm) S. aureus [84]
Dysidea granulosa Kavaratti Island, India (ND) Enterobacter sp. TTAG Proteobacteria Unidentified DOI (22 mm) S. aureus [85]
Petrosia ficiformis Paraggi, Ligurian Sea, Italy (8 m) Rhodococcus sp. E1 Actinobacteria Unidentified ND S. aureus [86]
Unidentified Atlantic coast, USA (ND) Kocuria palustris F-276,310; Kocuria marina F-276,345
Micrococcus yunnanensis F-256,446
Actinobacteria Kocurin MIC (0.25 µg/mL) methicillin-resistant Staphylococcus aureus (MRSA) [42,43]
Halichondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266183 MIC (0.78 µg/mL) MRSA [40,41]
Halichondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266184 MIC (0.39 µg/mL) MRSA [40,41]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Mayamycin IC50 (0.58 µg/mL) MRSA [45]
Melophus sp. Lau group, Fiji islands (10 m) Penicillium sp. FF001 Ascomycota Citrinin MIC (3.90 µg/mL) MRSA [57]
Halichondria panicea Bogil island, Korea (ND) Exophiala sp. Ascomycota Chlorohydroaspyrones A MIC (125 µg/mL) MRSA [60]
Chlorohydroaspyrones B MIC (62.5 µg/mL) MRSA
Callyspongia spp. Gulf of Mannar, India (ND) Pseudomonas spp. RHLB 12 Proteobacteria Chromophore compound DOI (4 mm) at 50 µM MRSA [87]
Xestospongia testudinaria Bidong Island, Malaysia (ND) Serratia marcescens IBRL USM 84 Proteobacteria Prodigiosin DOI (22.5 mm) MRSA [66]
Halichondria sp. West Coast of India (10 m) Bacillus licheniformis SAB1 Firmicutes Indole 3-phenylpropionic DOI (4–6 mm) MRSA [69]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Bacillus subtilis MMA7 Firmicutes Subtilomycin ND MRSA [71]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (23 mm) MRSA [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (27 mm) MRSA [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (17 mm) MRSA [77]
Axinella dissimilis Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio Ad30 Proteobacteria Unidentified ND MRSA [78]
Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Streptomyces sp. SM2 and SM4 Actinobacteria Unidentified ND MRSA [88]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (20 mm) community-associated MRSA [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (22 mm) community-associated MRSA [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (43 mm) community-associated MRSA [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (40 mm) community-associated MRSA [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (40 mm) community-associated MRSA [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (17 mm) community-associated MRSA [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (25 mm) community-associated MRSA [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (20 mm) community-associated MRSA [77]
Aplysina aerophoba Banyuls-sur-Mer, France (15 m) Bacillus subtilis A202 Firmicutes Iturin ND multi drug-resistant S. aureus [68]
Halichondria panicea Bogil island, Korea (ND) Exophiala sp. Ascomycota Chlorohydroaspyrones A MIC (125 µg/mL) multi drug-resistant S. aureus [60]
Chlorohydroaspyrones B MIC (125 µg/mL) multi drug-resistant S. aureus [60]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Bacillus subtilis MMA7 Firmicutes Subtilomycin ND heterogeneous vancomycin intermediate Staphylococcus aureus (hVISA) [71]
Axinella dissimilis Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio Ad30 Proteobacteria Unidentified ND hVISA [78]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Streptomyces sp. SM2 and SM4 Proteobacteria Unidentified ND hVISA [88]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Streptomyces sp. SM2 and SM4 Proteobacteria Unidentified ND vancomycin intermediate Staphylococcus aureus (VISA) [88]
Melophus sp. Lau group, Fiji islands (10 m) Penicillium sp. FF001 Ascomycota Citrinin MIC (0.97 µg/mL) rifampicin-resistant S.aureus [57]
Halichondria panicea Baltic Sea (ND) Streptomyces sp. HB202 Actinobacteria Mayamycin IC50 (0.14 µg/mL) Staphylococcus epidermidis [45]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Streptophenazines G IC50 (3.57 ± 0.21 µg/mL) S. epidermidis [89]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Streptophenazines K IC50 (6.16 ± 0.85 µg/mL) S. epidermidis [89]
Axinella corrugata Arvoredo Biological Marine Reserve, Brazil (ND) Penicillium sp. Ascomycota Dipeptide cis-cyclo(leucyl-tyrosyl) reducing 85% of biofilm formation at 1000 µg/mL S. epidermidis [90]
unidentified sponge Vizhijam coast (10–12 m) Aspergillus clavatus MFD15 Ascomycota 1H-1,2,4-Triazole-3-carboxaldehyde 5-methyl MIC (800 ± 10 µg/mL) S. epidermidis [91]
Spongia officinalis Southeast Coast India (10–15 m) Streptomyces sp. MAPS15 Actinobacteria 2-Pyrrolidone MIC (500 µg/mL) S. epidermidis PC5 [63]
Xestospongia testudinaria Bidong Island, Malaysia (ND) Serratia marcescens IBRL USM 84 Proteobacteria Prodigiosin DOI (<9 mm) S. epidermidis [66]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A184 Firmicutes Surfactin Iturin Fengycin ND S. epidermidis [68]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A190 Firmicutes Surfactin ND S. epidermidis [68]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (35 mm) S. epidermidis [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (30 mm) S. epidermidis [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (28 mm) S. epidermidis [77]
Dragmacidon reticulatus Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Dr31 Firmicutes Unidentified DOI (20 mm) S. epidermidis [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (45 mm) S. epidermidis [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (38 mm) S. epidermidis [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (25 mm) S. epidermidis [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (35 mm) S. epidermidis [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (30 mm) S. epidermidis [77]
Pseudoceratina clavata Heron Island, Australia (14 m) Salinispora sp. M102, M403, M412, M413, M414, SW10, SW15, SW17 Actinobacteria Unidentified DOI (<5 mm) S. epidermidis [79]
Pseudoceratina clavata Heron Island, Australia (14 m) Salinispora sp. SW02 Actinobacteria Unidentified DOI (>5 mm) S. epidermidis [79]
Callyspongia diffusa Bay of Bengal, India (10–15 m) Streptomyces sp. CPI 13 Actinobacteria Unidentified DOI (6.6 mm) S. epidermidis [92]
Micromonospora sp. CPI 12 Actinobacteria Unidentified DOI (6.6 mm) S. epidermidis [92]
Saccharomonospora sp. CPI 3 Actinobacteria Unidentified DOI (6.3 mm) S. epidermidis [92]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (25 mm) S. epidermidis 57s (susceptibile to amp, cip, pen, tet) [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (25 mm) S. epidermidis 57s [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (33 mm) S. epidermidis 57s [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (30 mm) S. epidermidis 57s [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (30 mm) S. epidermidis 57s [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (15 mm) S. epidermidis 57s [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (17 mm) S. epidermidis 57s [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (16 mm) S. epidermidis 57s [77]
Xestospongia testudinaria Weizhou coral reef, China (ND) Aspergillus sp. Ascomycota (Z)-5-(Hydroxymethyl)-2-(6′-methylhept-2′-en-2′-yl)phenol MIC (4.66 µg/mL) Staphylococcus albus [48]
Aspergiterpenoid A MIC (1.24 µg/mL)
(−)-5-(Hydroxymethyl)-2-(2′,6′,6′-trimethyltetrahydro-2H-pyran-2-yl)phenol MIC (1.26 µg/mL)
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (27 mm) Staphylococcus haemolyticus [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (27 mm) S. haemolyticus [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (35 mm) S. haemolyticus [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (40 mm) S. haemolyticus [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (40 mm) S. haemolyticus [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (38 mm) S. haemolyticus [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (40 mm) S. haemolyticus [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (43 mm) S. haemolyticus [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (19 mm) S. haemolyticus 109s (susceptible to amp, gen, oxa, pen) [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (15 mm) S. haemolyticus 109s [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (35 mm) S. haemolyticus 109s [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (31 mm) S. haemolyticus 109s [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (36 mm) S. haemolyticus 109s [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (23 mm) S. haemolyticus 109s [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (30 mm) S. haemolyticus 109s [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (20 mm) S. haemolyticus 109s [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (31mm) Staphylococcus hominis [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (28 mm) S. hominis [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (37 mm) S. hominis [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (41 mm) S. hominis [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (43 mm) S. hominis [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (23 mm) S. hominis [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (25 mm) S. hominis [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (24 mm) S. hominis [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (25 mm) Staphylococcus hominis 79s (susceptible to amp, pen) [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (27 mm) S. hominis 79s [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (20 mm) S. hominis 79s [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (35 mm) S. hominis 79s [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (30 mm) S. hominis 79s [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (25 mm) S. hominis 79s [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (25 mm) S. hominis 79s [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (28 mm) S. hominis 79s [77]
Xestospongia testudinaria Bidong Island, Malaysia (ND) Serratia marcescens IBRL USM 84 Proteobacteria Prodigiosin DOI (≤9 mm) Staphylococcus saprophyticus [66]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Mayamycin IC50 (3.71 µg/mL) Staphylococcus lentus [45]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB062 Actinobacteria Unidentified ND S. lentus [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB117 Actinobacteria Unidentified ND S. lentus [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB122 Actinobacteria Unidentified ND S. lentus [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB132 Actinobacteria Unidentified ND S. lentus [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB138 Actinobacteria Unidentified ND S. lentus [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB149 Actinobacteria Unidentified ND S. lentus [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB184 Actinobacteria Unidentified ND S. lentus [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB253 Actinobacteria Unidentified ND S. lentus [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB272 Actinobacteria Unidentified ND S. lentus [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB288 Actinobacteria Unidentified ND S. lentus [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB298 Actinobacteria Unidentified ND S. lentus [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB328 Actinobacteria Unidentified ND S. lentus [44]
Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB375 Actinobacteria Unidentified ND S. lentus [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB383 Actinobacteria Unidentified ND S. lentus [44]
Dendrilla nigra Southwest Coast of India (10-12 m) Nocardiopsis dassonvillei MAD08 Actinobacteria Unidentified MIC (600 µg/mL) Staphylococcus sp. PC8 [93]
Halichondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266183 MIC (1.56 µg/mL) Methicillin-Resistant Streptococcus epidermidis (MRSE) [40,41]
Halichondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266184 MIC (0.2 µg/mL) MRSE [40,41]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A202 Firmicutes Iturin ND Multi drug-resistant S. epidermidis [68]
Dysidea granulosa Kavaratti Island, India (ND) Enterobacter sp. TTAG Proteobacteria Unidentified DOI (23 mm), MIC crude extract (5 mg/mL) Streptococcus sp. [85]
Petrosia sp. Jeju island, Korea (20 m) Aspergillus versicolor Ascomycota Averantin MIC (0.78 µg/mL) Streptococcus pyogenes 308A [58]
Petrosia sp. Jeju island, Korea (20 m) Aspergillus versicolor Ascomycota Nidurufin MIC (3.13 µg/mL) Streptococcus pyogenes 308A [58]
Petrosia sp. Jeju island, Korea (20 m) Aspergillus versicolor Ascomycota Averantin MIC (3.13 µg/mL) Streptococcus pyogenes 77A [58]
Petrosia sp. Jeju island, Korea (20 m) Aspergillus versicolor Ascomycota Nidurufin MIC (6.25 µg/mL) Streptococcus pyogenes 77A [58]
Halichondria sp. West Coast of India (10 m) Bacillus licheniformis SAB1 Firmicutes Indole DOI (1–3 mm) Streptococcus pyogenes [69]
Halichondria sp. West Coast of India (10 m) Bacillus licheniformis SAB1 Firmicutes 3-Phenylpropionic DOI (4–6 mm) Streptococcus pyogenes [69]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Streptomyces sp. SM2 and SM4 Actinobacteria Unidentified ND Streptococcus pneumoniae [88]
Callyspongia diffusa Bay of Bengal, India (10–15 m) Saccharomonospora sp. CPI 9 Actinobacteria Unidentified ND haemolytic Streptococcus sp (6.3) [92]
Halichondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266183 MIC (1.56 µg/mL) Bacillus subtilis ATCC 633 [40,41]
Halichondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266184 MIC (1.56 µg/mL) B. subtilis ATCC 633 [40,41]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Mayamycin IC50 (3.71 µg/mL) B. subtilis [45]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Streptophenazines G IC50 (3.49 ± 0.38 µg/mL) B. subtilis [89]
Halichondria panacea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Streptophenazines K IC50 (9.18 ± 2.89 µg/mL) B. subtilis [89]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB084 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB095 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB096 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB105 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB107 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB116 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB117 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB118 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB122 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB132 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB138 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB181 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB184 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB253 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB272 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB298 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB328 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB375 Actinobacteria Unidentified ND B. subtilis [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB383 Actinobacteria Unidentified ND B. subtilis [44]
Callyspongia sp. Kyung-Po beach, Korea (12 m) Brevibacterium sp. KMD 003 Actinobacteria 6-Hydroxymethyl-1-phenazine-carboxamide MIC (5.06 µg/mL) B. subtilis [94]
Brevibacterium sp. KMD 003 1,6-Phenazinedimethanol MIC (4.80 µg/mL) B. subtilis [94]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Streptomyces sp. SM8 Actinobacteria Mixture Kitamycin A or B and Antimycin A3 or A7 MIC (7.42 µg/mL) B. subtilis [95]
Antimycin A2, A8, A11 or A17 MIC (9.40 µg/mL)
Antimycin A3 or A7 MIC (400 µg/mL)
Antimycin A2, A8, A11 or A17, antimycin A3 or A7 MIC (400 µg/mL)
Hymeniacidon perleve Bohai Sea, China (ND) Aspergillus versicolor MF359 Ascomycota 5-Methoxydihydrosterigmatocystin MIC (3.125 µg/mL) B. subtilis [56]
Hymeniacidon perleve Nanji island, China (ND) Pseudoalteromonas piscicida NJ6-3-1 Proteobacteria Norharman (beta-carboline alkaloid) MIC (50 µg/mL) B. subtilis [59]
Xestospongia testudinaria Weizhou coral reef, China (ND) Aspergillus sp. Ascomycota (−)-Sydonic acid MIC (0.66 µg/mL) B. subtilis [48]
(Z)-5-(Hydroxymethyl)-2-(6′-methylhept-2′-en-2′-yl)phenol MIC (2.33 µg/mL)
(−)-5-(Hydroxymethyl)-2-(2′,6′,6′-trimethyltetrahydro-2H-pyran-2-yl)phenol MIC (0.62 µg/mL)
Dysidea herbacea Koror, Republic Palau (1 m) Oscillatoria spongeliae Cyanobacteria 2-(2′,4′-Dibromophenyl)-4,6-dibromophenol ND B. subtilis [64]
Hyrtios altum Aragusuku island, Japan (ND) Vibrio sp. Proteobacteria Trisindoline DOI (17 mm) B. subtilis [65]
Xestospongia testudinaria Bidong Island, Malaysia (ND) Serratia marcescens IBRL USM 84 Proteobacteria Prodigiosin DOI (<9 mm) B. subtilis [66]
Niphates olemda Bali Bata National Park, Indonesia (ND) Curvularia lunata Ascomycota 1,3,8-Trihydroxy-6-methoxyanthraquinone (lunatin) DOI (9 mm) B. subtilis [70]
Bisanthraquinone cytoskyrin A DOI (12 mm) B. subtilis
Hymeniacidon perleve Nanji Island, China (ND) Pseudomonas sp. NJ6-3-1 Proteobacteria Unidentified 5 mm B. subtilis [74]
Axinella dissimilis Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio Ad30 Proteobacteria Unidentified ND B. subtilis [78]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. M102, M403, M412, M413, M414, SW02, SW10, SW 15 and SW 17 Actinobacteria Unidentified ND B. subtilis [79]
Dendrilla nigra Southeast coast of India (ND) Streptomyces sp. BTL7 Actinobacteria Unidentified DOI (15 mm) B. subtilis [80]
Mycale sp. Gulei Port, Fujian, China (ND) Bacillus sp. HNS004 HNS015; Firmicutes Unidentified DOI (8–10 mm) B. subtilis [81]
Mycale sp. Gulei Port, Fujian, China (ND) Pseudomonas sp. HNS021; HNS027; Vibrio sp. HNS038 Proteobacteria Unidentified DOI (8–10 mm) B. subtilis [81]
Mycale sp. Gulei Port, Fujian, China (ND) Labrenzia sp. HNS063; Streptomyces sp. HNS047; Nocardiopsis sp. HNS048, HNS055, HNS058; Cobetia sp. HNS023, Actinobacteria Unidentified DOI (8–10 mm) B. subtilis [81]
Mycale sp. Gulei Port, Fujian, China (ND) Bacillus sp. HNS005, HNS010, Firmicutes Unidentified DOI (10–15 mm) B. subtilis [81]
Mycale sp. Gulei Port, Fujian, China (ND) Streptomyces sp. HNS049, HNS056 Actinobacteria Unidentified DOI (10–15 mm) B. subtilis [81]
Mycale sp. Gulei Port, Fujian, China (ND) Vibrio sp. HNS022, HNS029; Firmicutes Unidentified DOI (15–30 mm) B. subtilis [81]
Mycale sp. Gulei Port, Fujian, China (ND) Streptomyces sp. HNS054 Actinobacteria Unidentified DOI (15–30 mm) B. subtilis [81]
Sigmadocia fibulatus Hare Island, India (5-10 m) Bacillus sp. SC3 Firmicutes Unidentified ND B. subtilis [96]
Amphilectus fucorum Lough Hyne, Ireland (8–15 m) Pseudovibrio sp. 113V
Pseudovibrio 83V1
Proteobacteria Unidentified ND B. subtilis [97]
Eurypon major Lough Hyne, Ireland (8–15 m) Pseudovibrio sp. 107L, 108L, 109L Proteobacteria Unidentified ND B. subtilis [97]
Suberites carnosus Lough Hyne, Co. Cork, Ireland (15 m) Arthrobacter sp. W13C11 Actinobacteria Unidentified ND B. subtilis [83]
Suberites carnosus Lough Hyne, Co. Cork, Ireland (15 m) Pseudovibrio sp. W13S4, W13S21, W13S23, W13S26, W13S31 Proteobacteria Unidentified ND B. subtilis [83]
Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Streptomyces sp. SM2 and SM4 Actinobacteria Unidentified ND B. subtilis [88]
Isodictya setifera Ross island, Antartica (30–40 m) Pseudomonasaeruginosa Proteobacteria Phenazine-1-carboxylic acid and phenazine-1-carboxamide MIC (<0.49 µg/mL) Bacillus cereus [55]
Xestospongia testudinaria Weizhou coral reef, China (ND) Aspergillus sp. Ascomycota (Z)-5-(Hydroxymethyl)-2-(6′-methylhept-2′-en-2′-yl)phenol MIC (2.33 µg/mL) B. cereus [48]
Xestospongia testudinaria Bidong Island, Malaysia (ND) Serratia marcescens IBRL USM 84 Proteobacteria Prodigiosin DOI (10–14 mm) B. cereus [66]
Dendrilla nigra Vizhinjam coast, India (10–15 m) Streptomyces sp. MSI051 Actinobacteria Unidentified MIC (46 ± 1.62 µg protein/mL) B. cereus [73]
Axinella dissimilis Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio Ad30 Proteobacteria Unidentified ND B. cereus [78]
Dendrilla nigra Southeast coast of India (ND) Streptomyces sp. BTL7 Actinobacteria Unidentified DOI (16 mm) B. cereus [80]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Streptomyces sp. SM2 and SM4 Actinobacteria Unidentified ND B. cereus [88]
Xestospongia testudinaria Bidong Island, Malaysia (ND) Serratia marcescens IBRL USM 84 Proteobacteria Prodigiosin DOI (10–14 mm) Bacillus licheniformis [66]
Xestospongia testudinaria Bidong Island, Malaysia (ND) Serratia marcescens IBRL USM 84 Proteobacteria Prodigiosin DOI (<9 mm) Bacillus thuringiensis [66]
unidentified South China Sea (10 m) Nocardiopsis sp. 13-33-15 and 13-12-13 Actinobacteria 1,6-Dihydroxyphenazine DOI (16 ± 0.5 mm) Bacillus mycoides SJ14 [67]
1,6-Dimethoxyphenazine DOI (20 ± 0.4 mm)
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A184 Firmicutes Surfactin iturin fengycin ND Bacillus megaterium [68]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A190 Firmicutes Surfactin ND B. megaterium [68]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A202 Firmicutes Iturin ND B. megaterium [68]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Bacillus subtilis MMA7 Firmicutes Subtilomycin ND B. megaterium [71]
Dysidea avara Mediterranean sea (ND) Actinokinespora sp. EG49 Actinobacteria 1,6-Dihydroxyphenazine (result of the co-culture) DOI (11 mm) Bacillus sp. P25 [98]
Spheciospongia vagabunda Red Sea (ND) Nocardiopsis sp. RV163
Callyspongia diffusa Bay of Bengal, India (10–15 m) Streptomyces sp. CPI 13 Actinobacteria Unidentified DOI (6.6 mm) Bacillus sp. [92]
Callyspongia diffusa Bay of Bengal, India (10–15 m) Micromonospora sp. CPI 12 Actinobacteria Unidentified DOI (8 mm) Bacillus sp. [92]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (19 mm) Enterococcus faecalis [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (17 mm) E. faecalis [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (32 mm) E. faecalis [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (11 mm), E. faecalis [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (12 mm), E. faecalis [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (14 mm) E. faecalis [77]
unidentified Rovinj, Croatia (3–20 m) Streptomyces sp. RV15 Actinobacteria Unidentified DOI (11 mm) E. faecalis [82]
unidentified Rovinj, Croatia (3–20 m) Microbacterium sp. EG69 Actinobacteria Unidentified DOI (9 mm) E. faecalis [82]
unidentified Rovinj, Croatia (3–20 m) Micromonospora sp. RV115 Actinobacteria Unidentified DOI (10 mm) E. faecalis [82]
unidentified Rovinj, Croatia (3–20 m) Rhodococcus sp. EG33 Actinobacteria Unidentified DOI (8 mm) E. faecalis [82]
Halocondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266183 MIC (0.1 µg/mL) E. faecalis CAY 04_1 [40,41]
Halocondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266184 MIC (0.025 µg/mL) E. faecalis CAY 04_1 [40,41]
Spheciospongia vagabunda Red Sea (ND) Micrococcus sp. EG45 Actinobacteria Microluside A MIC (9.55 µg/mL) E. faecalis JH212 [54]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (20 mm) E. faecalis 5AE (susceptible to van) [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (12 mm) E. faecalis 5AE [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (15 mm) E. faecalis 5AE [77]
Halocondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266183 MIC 0.2 µg/mL Enterococcus faecium CAY 09_1 [40,41]
Halocondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266184 MIC (0.05 µg/mL) E. faecium CAY 09_1 [40,41]
Halocondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266183 MIC (0.025 µg/mL) Vancomycin-Resistant E. faecium CAY 09_2 [40,41]
Halocondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266184 MIC (0.025 µg/mL) Vancomycin-Resistant E. faecium CAY 09_2 [40,41]
Melophus sp. Lau group, Fiji islands (10 m) Penicillium sp. FF001 Ascomycota Citrinin MIC (1.95 µg/mL) Vancomycin-resistant E. faecium [57]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Bacillus subtilis MMA7 Firmicutes Subtilomycin ND E. faecium [71]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (18 mm) E. faecium [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (21 mm) E. faecium [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (30 mm) E. faecium [77]
Dragmacidon reticulatus Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Dr31 Firmicutes Unidentified DOI (20 mm) E. faecium [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (23 mm) E. faecium [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (20 mm) E. faecium [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (22 mm) E. faecium [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (20 mm) E. faecium [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (15 mm) E. faecium [77]
Axinella dissimilis Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio Ad30 Proteobacteria Unidentified ND E. faecium [78]
Axinella dissimilis Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio Ad30 Proteobacteria Unidentified ND Vancomycin-resistant Enterococcus sp. [78]
Callyspongia sp. Kyung-Po beach, Korea (12 m) Brevibacterium sp. KMD 003 Actinobacteria 6-Hydroxymethyl-1-phenazine-carboxamide MIC (1.26 µg/mL) Enterococcus hirae [94]
1,6-Phenazinedimethanol MIC (1.20 µg/mL) E. hirae [94]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (22 mm) Enterobacter cloacae [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (25 mm) E. cloacae [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (18 mm) E. cloacae [77]
Callyspongia diffusa Southwest Coast of India (6–7 m) Shewanella algae VCDB KC623651 Proteobacteria Unidentified DOI (11mm) E. cloacae [99]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (19 mm) E. cloacae AE (susceptible to amp, cef, fox, tet) [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (12 mm) E. cloacae AE [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (23 mm) E. cloacae AE [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (20 mm) E. cloacae AE [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (20 mm) E. cloacae AE [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (28 mm) Enterobacter hafniae
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (21 mm) E. hafniae [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (23 mm) E. hafniae [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (18 mm) E. hafniae [77]
Axinella dissimilis Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio Ad30 Proteobacteria Unidentified ND Enterobacter aerogenes [78]
Xestospongia testudinaria Weizhou coral reef, China (ND) Aspergillus sp. Ascomycota (−)-Sydonic acid MIC (1.33 µg/mL Escherichia coli [48]
(Z)-5-(Hydroxymethyl)-2-(6′-methylhept-2′-en-2′-yl)phenol MIC (2.33 µg/mL)
Aspergiterpenoid A MIC (4.72 µg/mL
(−)-Sydonol MIC (5.04 µg/mL)
Halocondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266183 MIC (>100 µg/mL) E. coli JCM 5491 [40,41]
Halocondria japonica Iriomote island, Japan (ND) Bacillus cereus QNO3323 Firmicutes Thiopeptide YM-266184 MIC (>100 µg/mL) E. coli JCM 5491 [40,41]
unidentified sponge Vizhijam coast (10–12 m) Aspergillus clavatus MFD15 Ascomycota 1H-1,2,4-Triazole-3-carboxaldehyde 5-methyl MIC (800 ± 10 µg/mL) E. coli [91]
Spongia officinalis Southeast Coast India (10–15 m) Streptomyces sp. MAPS15 Actinobacteria 2-Pyrrolidone MIC (400 µg/mL) E. coli PC1 [63]
Dysidea herbacea Koror, Republic Palau (1 m) Oscillatoria spongeliae Cyanobacteria 2-(2′,4′-Dibromophenyl)-4,6-dibromophenol ND E. coli [64]
Hyrtios altum Aragusuku island, Japan (ND) Vibrio sp Proteobacteria Trisindoline DOI (16 mm) E. coli [65]
Xestospongia testudinaria Bidong Island, Malaysia (ND) Serratia marcescens IBRL USM 84 Proteobacteria Prodigiosin DOI (≤9 mm) E. coli [66]
unidentified South China Sea (10 m) Nocardiopsis sp. 13-33-15 and 13-12-13 Actinobacteria 1,6-Dihydroxyphenazine DOI (8 ± 0.4 mm) E. coli SJ42 [67]
unidentified South China Sea (10 m) Nocardiopsis sp. 13-33-15 and 13-12-13 Actinobacteria 1,6-Dimethoxyphenazine DOI (10 ± 0.6mm) E. coli SJ42 [67]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A184 Firmicutes Surfactin Iturin Fengycin ND E. coli [68]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A190 Firmicutes Surfactin ND E. coli [68]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A202 Firmicutes Iturin ND E. coli [68]
Niphates olemda Bali Bata National Park, Indonesia (ND) Curvularia lunata Ascomycota 1,3,8-Trihydroxy-6-methoxyanthraquinone (lunatin) DOI (11 mm) E. coli [70]
Niphates olemda Bali Bata National Park, Indonesia (ND) Curvularia lunata Ascomycota Bisanthraquinone cytoskyrin A DOI (11 mm) E. coli [70]
Niphates olemda Bali Bata National Park, Indonesia (ND) Curvularia lunata Ascomycota 1,3,8-Trihydroxy-6-methoxyanthraquinone (lunatin) DOI (10.5 mm) E.coli HBI-101 [70]
Niphates olemda Bali Bata National Park, Indonesia (ND) Curvularia lunata Ascomycota Bisanthraquinone cytoskyrin A DOI (9 mm) E.coli HBI-101 [70]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W64, W69, W89, W74 Proteobacteria Tropodithietic acid DOI (≥ 2 mm) E. coli [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. JIC5, JIC6, JIC17, W62, W65, W71, W99, WC43, W85, W78, W94, W96, WM31, WM33, WM34, WM40, WC13, WC21, WC22, WC30, WC32, WC41, HC6, HMMA3 Proteobacteria Unidentified DOI (≥2 mm) E. coli [72]
Dendrilla nigra Southwest Coast of India Nocardiopsis dassonvillei MAD08 Actinobacteria Unidentified MIC (300 µg/mL) E. coli PC1 [93]
Hymeniacidon perleve Nanji Island, China (ND) Pseudomonas sp. NJ6-3-1 Proteobacteria Unidentified DOI (1–3 mm) E. coli [74]
Callyspongia spp Kovalam Coast, India (5–10 m) Aspergillus flavus GU815344 Ascomycota Unidentified DOI (42 mm) E. coli [75]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (25 mm) E. coli [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (15 mm) E. coli [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (22 mm) E. coli [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Proteobacteria Unidentified DOI (18 mm) E. coli [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Proteobacteria Unidentified DOI (16 mm) E. coli [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (12 mm) E. coli [77]
Axinella dissimilis Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio Ad30 Proteobacteria Unidentified ND E. coli [78]
Dendrilla nigra Southeast coast of India (ND) Streptomyces sp. BTL7 Actinobacteria Unidentified DOI (16 mm) E. coli [80]
Mycale sp. Gulei Port, Fujian, China (ND) Bacillus sp. HNS005 Firmicutes Unidentified DOI (8–10 mm) E. coli [81]
Mycale sp. Gulei Port, Fujian, China (ND) Vibrio sp. HNS038; Proteobacteria Unidentified DOI (8–10 mm) E. coli [81]
Mycale sp. Gulei Port, Fujian, China (ND) Streptomyces sp. HNS047; Nocardiopsis sp. HNS051, HNS055, HNS056 Actinobacteria
Mycale sp. Gulei Port, Fujian, China (ND) Streptomyces sp. HNS054; Nocardiopsis sp. HNS058 Actinobacteria Unidentified DOI (10–15 mm) E. coli [81]
Callyspongia diffusa Bay of Bengal, India (10–15 m) Micromonospora sp. CPI 12 Actinobacteria Unidentified DOI (7.5m ) E. coli [92]
Sigmadocia fibulatus Hare Island, India (5-10 m) Bacillus sp. SC3 Firmicutes Unidentified DOI (26 mm) E. coli [96]
Aplysina aerophoba and Aplysina cavernicola Marseille and Banyuls sur Mer, France (ND) Bacillus SB8, SB17 Firmicutes Unidentified DOI (12–16 mm) E. coli [84]
Aplysina aerophoba and Aplysina cavernicola Marseille and Banyuls sur Mer, France (ND) Enterococcus SB91 Proteobacteria Unidentified DOI (12–16 mm) E. coli [84]
Aplysina aerophoba and Aplysina cavernicola Marseille and Banyuls sur Mer, France (ND) Arthrobacter SB95 Actinobacteria Unidentified DOI (12–16 mm) E. coli [84]
Aplysina aerophoba and Aplysina cavernicola Marseille and Banyuls sur Mer, France (ND) unidentified low G + C Gram positive SB122 and SB144, Unidentified Unidentified DOI (12–16 mm) E. coli [84]
Aplysina aerophoba and Aplysina cavernicola Marseille and Banyuls sur Mer, France (ND) α-Proteobacteria SB6, SB55, SB63, SB89, SB156, SB197, SB202, SB207, SB214, Proteobacteria Unidentified DOI (12–16 mm) E. coli [84]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB107 Actinobacteria Unidentified ND E. coli [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB132 Actinobacteria Unidentified ND E. coli [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB253 Actinobacteria Unidentified ND E. coli [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB298 Actinobacteria Unidentified ND E. coli [44]
Amphilectus fucorum Lough Hyne, Ireland (8–15 m) Pseudovibrio sp. 117V, 115 V and 112 V Proteobacteria Unidentified ND E. coli [97]
Amphilectus fucorum Lough Hyne, Ireland (8–15 m) Pseudovibrio sp. 113V Proteobacteria Unidentified ND E. coli [97]
Eurypon major Lough Hyne, Ireland (8–15 m) Pseudovibrio sp. 107L, 108L, 109L Proteobacteria Unidentified ND E. coli [97]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Streptomyces sp. SM2 and SM4 Actinobacteria Unidentified DOI (25 mm) E. coli [88]
Dysidea granulosa Kavaratti Island, India (ND) Enterobacter sp. TTAG Proteobacteria Unidentified ND E. coli [85]
Callyspongia diffusa Southwest Coast of India (6–7 m) Shewanella algae VCDB KC623651 Proteobacteria Unidentified DOI (10 mm) E. coli [99]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (20 mm) E. coli 54AE (susceptible to amp, chl, sxt, tet) [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (17 mm) E. coli 54AE [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (20 mm) E. coli 54AE [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (35 mm) E. coli 54AE [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (39 mm) E. coli 54AE [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (15 mm) E. coli 54AE [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (21 mm) E. coli 54AE [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (25 mm) E. coli 54AE [77]
Petrosia ficiformis Paraggi, Ligurian Sea, Italy (8 m) Pseudoalteromonas sp. F6 Proteobacteria Unidentified ND Escherichia faecalis [86]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Mayamycin IC50 (1.16 µg/mL) Klebsiella pneumoniae [45]
Spongia officinalis Southeast Coast India (10–15 m) Streptomyces sp. MAPS15 Actinobacteria 2-Pyrrolidone MIC (700 µg/mL) K. pneumonia PC7 [63]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (25 mm) K. pneumoniae [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Actinobacteria Unidentified DOI (24 mm) K. pneumoniae [77]
Dendrilla nigra Southeast coast of India (ND) Streptomyces sp. BTL7 Actinobacteria Unidentified DOI (<10 mm) K. pneumoniae [80]
Callyspongia diffusa Bay of Bengal, India (10–15 m) Streptomyces sp. CPI 13 Actinobacteria Unidentified DOI (9.2 mm) K. pneumoniae [92]
Callyspongia diffusa Bay of Bengal, India (10–15 m) Saccharomonospora sp. CPI 3 Actinobacteria Unidentified DOI (6.3 mm) K. pneumoniae [92]
Dysidea granulosa Cagarras Archipelago, Brazil (4–20 m) Enterobacter sp. TTAG Proteobacteria Unidentified DOI (22 mm) K. pneumoniae [85]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (18 mm) K. pneumoniae 52 AE [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (15 mm) K. pneumoniae 52 AE [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (21 mm) K. pneumoniae 52 AE [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (16 mm) K. pneumoniae 19AE (susceptible to amp, atm, caz, cpd, fox) [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (20 mm) K. pneumoniae 19AE [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (32 mm) K. pneumoniae 19AE [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (20 mm) Neisseria gonorrhoeae [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (27 mm) N. gonorrhoeae [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (52 mm) N. gonorrhoeae [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (28 mm) N. gonorrhoeae [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (29 mm) N. gonorrhoeae [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (24 mm) N. gonorrhoeae 4277 (susceptible to pen) [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (24 mm) N. gonorrhoeae 4277 [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (32 mm) N. gonorrhoeae 4277 [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (32 mm) N. gonorrhoeae 4277 [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (32 mm) N. gonorrhoeae 4277 [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (24 mm) N. gonorrhoeae 4957 (susceptible to cip) [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (29 mm) N. gonorrhoeae 4957 [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (36 mm) N. gonorrhoeae 4957 [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (23 mm) N. gonorrhoeae 4957 [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (23 mm) N. gonorrhoeae 4957 [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (20 mm) N. gonorrhoeae 5728 (cip, pen, tet) [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (19 mm) N. gonorrhoeae 5728 [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (46 mm) N. gonorrhoeae 5728 [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (29 mm) N. gonorrhoeae 5728 [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (32 mm) N. gonorrhoeae 5728 [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (18 mm) N. gonorrhoeae 5729 (susceptible to azm, pen, tet) [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (16 mm) N. gonorrhoeae 5729 [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (35 mm) N. gonorrhoeae 5729 [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (25 mm) N. gonorrhoeae 5729 [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (32 mm) N. gonorrhoeae 5729 [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (20 mm) N. gonorrhoeae 6002 (susceptible to tet) [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (26 mm) N. gonorrhoeae 6002 [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (28 mm) N. gonorrhoeae 6002 [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (28 mm) N. gonorrhoeae 6002 [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (26 mm) N. gonorrhoeae 6002 [77]
Haliclona occulata Gulf of Mannar, India (ND) Bacillus licheniformis T6-1 Firmicutes Fluorophore compound DOI (6 mm) at 50 µM Salmonella typhi [87]
Dysidea granulosa Kavaratti Island, India (ND) Enterobacter sp. TTAG Proteobacteria Unidentified DOI (19 mm) S. typhi [85]
Callyspongia diffusa Southwest Coast of India (6–7 m) Shewanella algae VCDB KC623651 Proteobacteria Unidentified DOI (11 mm) S. typhi [99]
Dendrilla nigra Southeast coast of India (ND) Streptomyces sp. BTL7 Actinobacteria Unidentified DOI (16 mm) S. typhi [80]
Axinella dissimilis Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio Ad30 Proteobacteria Unidentified ND Salmonella typhimurium [78]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W64, W69, W89, W74 Proteobacteria Tropodithietic acid DOI (≥2 mm) S. typhimurium [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. JIC5, W63, W65, W71, W99, W96, WM40, WC32, WC41, HC6 Proteobacteria Unidentified DOI (≥2 mm) S. typhimurium [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W10, W62, WC43, W85, W78, W94, WM31, WM34, WC13, WC21, WC30 Proteobacteria Unidentified DOI (≥1 mm) S. typhimurium [72]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (21 mm) Salmonella enterica [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (17 mm) S. enterica [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (25 mm) S. enterica [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (14 mm) S. enterica [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (12 mm) S. enterica [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (14 mm) S. enterica [77]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Mayamycin IC50 (1.16 µg/mL) Pseudomonas aeruginosa [45]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40, H41 and Pseudomonas aeruginosa H51 Proteobacteria Diketopiperazine cyclo-(l-Leu-l-Pro) MIC (512 µg/mL ) P. aeruginosa [62]
Halichondria sp. West Coast of India (10 m) Bacillus licheniformis SAB1 Firmicutes Indole DOI (4–6 mm) P. aeruginosa [69]
Halichondria sp. West Coast of India (10 m) Bacillus licheniformis SAB1 Firmicutes 3-Phenylpropionic DOI (4–6 mm) P. aeruginosa [69]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (23 mm) P. aeruginosa [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (20 mm) P. aeruginosa [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (35 mm) P. aeruginosa [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (35 mm) P. aeruginosa [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (30 mm) P. aeruginosa [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (30 mm) P. aeruginosa [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (22 mm) P. aeruginosa [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (30 mm) P. aeruginosa [77]
Axinella dissimilis Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio Ad30 Proteobacteria Unidentified ND P. aeruginosa [78]
Dendrilla nigra Southeast coast of India (ND) Streptomyces sp. BTL7 Actinobacteria Unidentified DOI (21 mm) P. aeruginosa [80]
Callyspongia diffusa Bay of Bengal, India (10–15 m) Streptomyces sp. CPI 13 Actinobacteria Unidentified DOI (7.7 mm) P. aeruginosa [92]
Callyspongia diffusa Bay of Bengal, India (10–15 m) Micromonospora sp. CPI 12 Actinobacteria Unidentified DOI (6.9 mm) P. aeruginosa [92]
Callyspongia diffusa Bay of Bengal, India (10–15 m) Saccharomonospora sp. CPI 9 Actinobacteria Unidentified DOI (6.3 mm) P. aeruginosa [92]
Callyspongia diffusa Bay of Bengal, India (10–15 m) Saccharomonospora sp. CPI 3 Actinobacteria Unidentified DOI (6.3 mm) P. aeruginosa [92]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (32 mm) P. aeruginosa 3AE (susceptible to atm, tzp) [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (20 mm) P. aeruginosa 3AE [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (14 mm) P. aeruginosa 3AE [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (12 mm) P. aeruginosa 3AE [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (15 mm) P. aeruginosa 3AE [77]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB107 Actinobacteria Unidentified ND Pseudomonas fluorescens [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB132 Actinobacteria Unidentified ND P. fluorescens [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Unidentified ND P. fluorescens [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB107 Actinobacteria Unidentified ND Pseudomonas syringae [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB138 Actinobacteria Unidentified ND P. syringae [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB272 Actinobacteria Unidentified ND P. syringae [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB298 Actinobacteria Unidentified ND P. syringae [44]
Callyspongia sp. Kyung-Po beach, Korea (12 m) Brevibacterium sp. KMD 003 Actinobacteria 6-Hydroxymethyl-1-phenazine- carboxamide MIC (1.26 µg/mL) Micrococcus luteus [94]
1,6-Phenazinedimethanol MIC (1.20 µg/mL) M. luteus [94]
Isodictya setifera Ross island, Antartica (30–40 m) Pseudomonas aeruginosa Proteobacteria Phenazine-1-carboxylic acid and phenazine-1-carboxamide MIC (>4.99 µg/mL) M. luteus [55]
Dendrilla nigra Southeast coast of India (ND) Streptomyces sp. BTL7 Actinobacteria Unidentified DOI (19 mm), MIC (44 g protein/mL) M. luteus [80]
Callyspongia diffusa Bay of Bengal, India (10–15 m) Saccharomonospora sp. CPI 9 Actinobacteria Unidentified DOI (6.6 mm) M. luteus [92]
Callyspongia diffusa Bay of Bengal, India (10–15 m) Saccharomonospora sp. CPI 3 Actinobacteria Unidentified DOI (6.6 mm ) M. luteus [92]
unidentified South China Sea (10 m) Nocardiopsis sp. 13-33-15 and 13-12-13 Actinobacteria 1,6-Dihydroxyphenazine DOI (18 ± 0.9 mm) M. luteus SJ47 [67]
unidentified South China Sea (10 m) Nocardiopsis sp. 13-33-15 and 13-12-13 Actinobacteria 1,6-Dimethoxyphenazine DOI (23 ± 0.5 mm) M. luteus SJ47 [67]
Xestospongia testudinaria Weizhou coral reef, China (ND) Aspergillus sp. Ascomycota (−)-Sydonic acid MIC (5.33 µg/mL) Micrococcus tetragenus [48]
Xestospongia testudinaria Weizhou coral reef, China (ND) Aspergillus sp. Ascomycota (Z)-5-(Hydroxymethyl)-2-(6′-methylhept-2′-en-2′-yl)phenol MIC (2.33 µg/mL) M. tetragenus [48]
Xestospongia testudinaria Weizhou coral reef, China (ND) Aspergillus sp. Ascomycota Aspergiterpenoid A MIC (2.36 µg/mL) M. tetragenus [48]
Xestospongia testudinaria Weizhou coral reef, China (ND) Aspergillus sp. Ascomycota (−)-Sydonol MIC (0.32 µg/mL), M. tetragenus [48]
Xestospongia testudinaria Bidong Island, Malaysia (ND) Serratia marcescens IBRL USM 84 Proteobacteria Prodigiosin DOI (≤9 mm) Micrococcus sp. [66]
Petrosia ficiformis Paraggi, Ligurian Sea, Italy (8 m) Rhodococcus sp. E1 Actinobacteria Unidentified ND Micrococcus sp. [86]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Mayamycin IC50 (3.45 µg/mL) Brevibacterium epidermidis [45]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Mayamycin IC50 (3.89 µg/mL) Dermabacter hominis [45]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Mayamycin IC50 (14.48 µg/mL) Propionibacterium acnes [45]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Mayamycin IC50 (13.92 µg/mL) Xanthomonas campestris [45]
Dysidea tupha Rovinj, Croatia (ND) Streptomyces sp. RV15 Actinobacteria Naphthacene glycoside SF2446A2 IC50 (2.81 ± 0.24 µg/mL) Chlamydia trachomatis [46]
unidentified ND Trichoderma sp. 05FI48 Ascomycota Trichoderin A MIC (0.1 µg/mL) Mycobacterium smegmatis [49]
unidentified ND Trichoderma sp. 05FI48 Ascomycota Trichoderin A1 MIC (1.56 µg/mL) M. smegmatis [49]
unidentified ND Trichoderma sp. 05FI48 Ascomycota Trichoderin B MIC (0.63 µg/mL) M. smegmatis [49]
unidentified ND Trichoderma sp. 05FI48 Ascomycota Trichoderin A MIC (0.02 µg/mL) Mycobacterium bovis BCG [49]
unidentified ND Trichoderma sp. 05FI48 Ascomycota Trichoderin A1 MIC (0.16 µg/mL) M. bovis BCG [49]
unidentified ND Trichoderma sp. 05FI48 Ascomycota Trichoderin B MIC (0.02 µg/mL) M. bovis BCG [49]
unidentified ND Trichoderma sp. 05FI48 Ascomycota Trichoderin A MIC (0.12 µg /mL) Mycobacterium tuberculosis H37rv [49]
unidentified ND Trichoderma sp. 05FI48 Ascomycota Trichoderin A1 MIC (2.0 µg/mL) M. tuberculosis H37rv [49]
unidentified ND Trichoderma sp. 05FI48 Ascomycota Trichoderin B MIC (0.13 µg/mL) M. tuberculosis H37rv [49]
Xestospongia testudinaria Weizhou coral reef, China (ND) Aspergillus sp. Ascomycota (−)-Sydonic acid MIC (2.66 µg/mL) Vibrio parahaemolyticus [48]
Asbestopluma hypogea La Ciotat, France (17 m) Streptomyces sp. S1CA Actinobacteria Unidentified ND V. parahaemolyticus [100]
Mycale sp. Gulei Port, Fujian, China (ND) Bacillus sp. HNS010 Firmicutes Unidentified DOI (8–10 mm) V. parahaemolyticus [81]
Mycale sp. Gulei Port, Fujian, China (ND) Cobetia sp. HNS023; Nocardiopsis HNS055; HNS058 Actinobacteria Unidentified DOI (8–10 mm) V. parahaemolyticus [81]
Mycale sp. Gulei Port, Fujian, China (ND) Streptomyces sp. HNS054 Actinobacteria Unidentified DOI (10–15 mm) V. parahaemolyticus [81]
Phorbas tenacior Mediterranean Sea, Marseille, France (15 m) Citricoccus sp.P1S7 Actinobacteria Unidentified DOI (3–6 mm) V. parahaemolyticus [101]
Phorbas tenacior Mediterranean Sea, Marseille, France (15 m) Pseudovibrio sp. P1Ma4 and Vibrio sp. P1MaNal1 Proteobacteria Unidentified DOI (2–3 mm) V. parahaemolyticus [101]
Xestospongia testudinaria Weizhou coral reef, China (ND) Aspergillus sp. Ascomycota (−)-Sydonic acid MIC (1.33 µg/mL) Vibrio anguillarum [48]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Bacillus subtilis MMA7 Firmicutes Subtilomycin ND V. anguillarum [71]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W64, Proteobacteria Tropodithietic acid DOI (≥4 mm) V. anguillarum [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W69, W89, Proteobacteria Tropodithietic acid DOI (≥2 mm) V. anguillarum [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W74 Proteobacteria Tropodithietic acid DOI (≥1 mm) V. anguillarum [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. JIC5, W65, W99, W85, WM31, WM34, HC6 Proteobacteria Unidentified DOI (≥4 mm) V. anguillarum [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. JIC6, JIC17, WM33, WC15, WC22 Proteobacteria Unidentified DOI (≥1 mm) V. anguillarum [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W62, W71, WC43, W78, W94,W96, WM40, WC13, WC21, WC30, WC32, WC41, HMMA3 Proteobacteria Unidentified DOI (≥2 mm) V. anguillarum [72]
Phorbas tenacior Mediterranean Sea, Marseille, France (15 m) Citricoccus sp.P1S7 Actinobacteria Unidentified DOI (3–6 mm) V. anguillarum [101]
Callyspongia diffusa Southwest Coast of India (6–7 m) Shewanella algae VCDB KC623651 Proteobacteria Unidentified DOI (10 mm) Vibrio anguillarum [99]
Dendrilla nigra Southeast coast of India (ND) Streptomyces sp. BTL7 Actinobacteria Unidentified DOI (15 mm), MIC (176 g protein/mL) Vibrio fisheri [80]
Phorbas tenacior Mediterranean Sea, Marseille, France (15 m) Citricoccus sp.P1S7 Actinobacteria Unidentified DOI (3–6 mm) Vibrio algynoliticus [101]
Dysidea herbacea Koror, Republic Palau (1 m) Oscillatoria spongeliae Cyanobacteria 2-(2′,4′-Dibromophenyl)-4,6-dibromophenol ND Vibrio harveyi, [64]
Halichondria sp. West Coast of India (10 m) Bacillus licheniformis SAB1 Firmicutes 4,4′-Oxybis(3-phenylpropionic acid) DOI (4–6 mm) Vibrio cholerae [69]
Mycale sp. Gulei Port, Fujian, China (ND) Vibrio sp. HNS022, HNS029; Streptomyces sp. HNS049, HNS054, HNS056; Nocardiopsis sp. HNS055 Proteobacteria Unidentified DOI (8–10 mm) Vibrio diabolicus [81]
Callyspongia diffusa Southwest Coast of India (6–7 m) Shewanella algae VCDB KC623651 Proteobacteria Unidentified DOI (14 mm) Vibrio fluvialis [99]
Asbestopluma hypogea La Ciotat, France (17 m) Streptomyces sp. S1CA Actinobacteria Unidentified ND Vibrio sp. S2SW [100]
Asbestopluma hypogea La Ciotat, France (17 m) Streptomyces sp. S1CA Actinobacteria Unidentified ND Vibrio sp. S3SW [100]
Xestospongia testudinaria Bidong Island, Malaysia (ND) Serratia marcescens IBRL USM 84 Proteobacteria Prodigiosin DOI (10-14 mm) Agrobacterium tumefaciens [66]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A184 Firmicutes Surfactin iturin fengycin ND tumefaciens [68]
Hymeniacidon perleve Nanji Island, China (ND) Pseudomonas sp. NJ6-3-1 Proteobacteria Unidentified DOI (3–5 mm) tumefaciens [74]
Xestospongia testudinaria Bidong Island, Malaysia (ND) Serratia marcescens IBRL USM 84 Proteobacteria Prodigiosin DOI (≤9 mm) Acinetobacter anitratus [66]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (20 mm) baumanii [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (20 mm) baumanii [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (19 mm) Acinetobacter calcoaceticus [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (18 mm) calcoaceticus [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (30 mm) calcoaceticus [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (35 mm) calcoaceticus [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (30 mm) calcoaceticus [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (18 mm) calcoaceticus [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (23 mm) calcoaceticus [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Firmicutes Unidentified DOI (23 mm) calcoaceticus [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (45 mm) Acinetobacter sp [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (45 mm) Acinetobacter sp [77]
Halichondria sp. West Coast of India (10 m) Bacillus licheniformis SAB1 Firmicutes Indole DOI (1–3 mm) Acinetobacter sp. [69]
Halichondria sp. West Coast of India (10 m) Bacillus licheniformis SAB1 Firmicutes 3-Phenylpropionic DOI (4–6 mm) Acinetobacter sp [69]
Xestospongia testudinaria Bidong Island, Malaysia (ND) Serratia marcescens IBRL USM 84 Proteobacteria Prodigiosin DOI (≤9 mm) Erwinia sp [66]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A184 Firmicutes Surfactin Iturin Fengycin ND Clavibacter michiganensis [68]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A190 Firmicutes Surfactin ND Clavibacter michiganensis [68]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A202 Firmicutes Iturin ND Clavibacter michiganensis [68]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A184 Firmicutes Surfactin Iturin Fengycin ND Proteus vulgaris [68]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A190 Firmicutes Surfactin ND Proteus vulgaris [68]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A202 Firmicutes Iturin ND Proteus vulgaris [68]
Callyspongia diffusa Southwest Coast of India (6–7 m) Shewanella algae VCDB KC623651 Proteobacteria Unidentified DOI (10 mm) Proteus vulgaris [99]
Callyspongia diffusa Bay of Bengal, India (10–15 m) Micromonospora sp. CPI 12 Actinobacteria Unidentified DOI (8 mm) Proteus mirabilis [92]
Callyspongia diffusa Bay of Bengal, India (10–15 m) Saccharomonospora sp. CPI 9 Actinobacteria Unidentified DOI (6 mm Proteus mirabilis [92]
Callyspongia diffusa Bay of Bengal, India (10–15 m) Saccharomonospora sp. CPI 3 Actinobacteria Unidentified DOI (6 mm) Proteus mirabilis [92]
Dysidea avara Mediterranean sea (ND) Actinokinespora sp. EG49 Actinobacteria 1,6-Dihydroxyphenazine (result of co-culture) DOI (15 mm) Actinokinespora sp. EG49 [98]
Spheciospongia vagabunda Red Sea (ND) Nocardiopsis sp. RV163 Actinobacteria
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Bacillus subtilis MMA7 Firmicutes Subtilomycin ND Listeria monocytogenes [71]
Axinella dissimilis Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio Ad30 Proteobacteria Unidentified ND Listeria monocytogenes [78]
Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Streptomyces sp. SM2 and SM4 Actinobacteria Unidentified ND Listeria monocytogenes [88]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Bacillus subtilis MMA7 Firmicutes Subtilomycin ND Listeria innocua [71]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Bacillus subtilis MMA7 Firmicutes Subtilomycin ND Clostridium sporogenes [71]
Axinella dissimilis Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio Ad30 Proteobacteria Unidentified ND Clostridium perfringens [78]
Axinella dissimilis Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio Ad30 Proteobacteria Unidentified ND Clostridium difficile [78]
Dendrilla nigra Southeast coast of India (15 m) Streptomyces sp. BTL7 Actinobacteria Unidentified DOI (10 mm) Clostridium botulinum [80]
Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Streptomyces sp. SM2 and SM4 Actinobacteria Unidentified ND Clostridium difficile [88]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Bacillus subtilis MMA7 Firmicutes Subtilomycin ND Lactobacillus lactis [71]
Callyspongia diffusa Southwest Coast of India (6–7 m) Shewanella algae VCDB KC623651 Firmicutes Unidentified DOI (10 mm) L. lactis [99]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Bacillus subtilis MMA7 Firmicutes Subtilomycin ND Aeromonas hydrophila [71]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Bacillus subtilis MMA7 Firmicutes Subtilomycin ND Alteromonas sp. [71]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W64, W69, W89, W74 Proteobacteria Tropodithietic acid DOI (≥4 mm) Yersinia ruckerri [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. JIC5, JIC17, W10, W62, W63, W65, W71, W99, W85, W96, WM31, WM34, WM40, WC13, WC22, WC30, WC32, WC41, HC6 Proteobacteria Unidentified DOI (≥4 mm) Y. ruckerri [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. WC43, W78, W94,WM33, WC21, HMMA3 Proteobacteria Unidentified DOI (≥4 mm) Y. ruckerri [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. JIC6, WC15 Proteobacteria Unidentified DOI (≥1 mm) Y. ruckerri [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W64, W69, W89 Proteobacteria Tropodithietic acid DOI (≥4 mm) Edwardsialla tarda [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W74 Proteobacteria Tropodithietic acid DOI (≥2 mm) E. tarda [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. JIC5, W63, W99 Proteobacteria Unidentified DOI (≥4 mm) E. tarda [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. JIC6, JIC17, W10, W62, W65, W71, W85, W96, WM31,WM34, WM40, WC13, WC32, WC41, HC6 Proteobacteria Unidentified DOI (≥2 mm) E. tarda [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W78, W94, WM33, WC21, WC22, WC30, HMMA3 Proteobacteria Unidentified DOI (≥1 mm) E. tarda [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W64, W74 Proteobacteria Tropodithietic acid DOI (≥4 mm) Morganella morganii [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W69, W89, Proteobacteria Tropodithietic acid DOI (≥ 2 mm) M. morganii [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. JIC5, W62, W65, W71, W99, W78, WM34, HC6 Proteobacteria Unidentified DOI (≥4 mm) M. morganii [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. JIC17, W94, W96, WM40, WC13, WC21, WC32, WC41 Proteobacteria Unidentified DOI (≥2 mm) M. morganii [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. JIC6, W10, WC43, W85, WM31, WC15, WC22,WC30, HMMA3 Proteobacteria Unidentified DOI (≥1 mm) M. morganii [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W64, W69, W89 Proteobacteria Tropodithietic acid DOI (≥2 mm) Pandoraea sputorum [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W74 Proteobacteria Tropodithietic acid DOI (≥1 mm) P. sputorum [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W63 Proteobacteria Unidentified DOI (4 mm) P. sputorum [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. W62, WM40 Proteobacteria Unidentified DOI (≥2 mm) P. sputorum [72]
Polymastia boletiformis, Axinella dissimilis and Haliclona simulans Gurraig Sound, Kilkieran Bay, Ireland (15 m) Pseudovibrio sp. JIC5, JIC6, JIC17, W10, W65, W71, W99, WC43, W85, W78, W96, WM34, WC32, HC6 Proteobacteria Unidentified DOI (≥1 mm) P. sputorum [72]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (23 mm) Corynebacterium fimi [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (26 mm) Corynebacterium fimi [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (43 mm) Corynebacterium fimi [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Virgibacillus pantothenticus H31 Firmicutes Unidentified DOI (17 mm) Corynebacterium fimi [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Bacillus flexus H42 Firmicutes Unidentified DOI (21 mm) Corynebacterium fimi [77]
Dragmacidon reticulatus Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Dr31 Firmicutes Unidentified DOI (20 mm) Corynebacterium fimi [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc31 Firmicutes Unidentified DOI (46 mm) Corynebacterium fimi [77]
Petromica citrina Cagarras Archipelago, Brazil (4–20 m) Bacillus pumilus Pc32 Firmicutes Unidentified DOI (42 mm) Corynebacterium fimi [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (31 mm) Corynebacterium fimi [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (24 mm) Corynebacterium fimi [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm52 Proteobacteria Unidentified DOI (15 mm) Corynebacterium fimi [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (34 mm) Corynebacterium fimi [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (18 mm) Serratia marcescens [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (17 mm) S. marcescens [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (20 mm) S. marcescens [77]
Clathrina aurea Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Ca31 Proteobacteria Unidentified DOI (13 mm) Stenotrophomonas maltophilia [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (13 mm) S. maltophilia [77]
Mycale microsigmatosa Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio denitrificans Mm37 Proteobacteria Unidentified DOI (15 mm) S. maltophilia [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H40 Proteobacteria Unidentified DOI (19 mm) Citrobacter freundii [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas fluorescens H41 Proteobacteria Unidentified DOI (16 mm) C. freundii [77]
Haliclona sp. Cagarras Archipelago, Brazil (4–20 m) Pseudomonas aeruginosa H51 Proteobacteria Unidentified DOI (26 mm) C. freundii [77]
Paraleucilla magna Cagarras Archipelago, Brazil (4–20 m) Pseudovibrio ascidiaceicola Pm31 Proteobacteria Unidentified DOI (10 mm) C. freundii [77]
Xestospongia testudinaria Weizhou coral reef, China (ND) Aspergillus sp. Ascomycota (−)-Sydonic acid MIC (0.66 µg/mL) Sarcina lutea [48]
Dysidea herbacea Koror, Republic Palau (1 m) Oscillatoria spongeliae Cyanobacteria 2-(2′,4′-Dibromophenyl)-4,6-dibromophenol ND Synechococcus sp. [64]
Asbestopluma hypogea La Ciotat, France (17 m) Streptomyces sp. S1CA Actinobacteria Unidentified ND Ruegeria sp. S13SW [100]
Asbestopluma hypogea La Ciotat, France (17 m) Streptomyces sp. S1CA Actinobacteria Unidentified ND Sulfitobacter sp. S16SW [100]
Asbestopluma hypogea La Ciotat, France (17 m) Streptomyces sp. S1CA Actinobacteria Unidentified ND Pseudoalteromonas distincta [100]
Phorbas tenacior Mediterranean Sea, Marseille, France (15 m) Citricoccus sp.P1S7 Actinobacteria Unidentified 3–6 mm P. distincta [101]
Phorbas tenacior Mediterranean Sea, Marseille, France (15 m) Pseudovibrio sp. P1Ma4 and Vibrio sp. P1MaNal1 Proteobacteria Unidentified 2–3 mm P. distincta [101]
Dendrilla nigra Vizhinjam coast, India (10–15 m) Streptomyces sp. MSI051 Actinobacteria Unidentified MIC (32 ± 0.61 µg protein/mL) unidentified biofilm bacterium EB1 [73]
Dendrilla nigra Vizhinjam coast, India (10–15 m) Streptomyces sp. MSI051 Actinobacteria Unidentified MIC (34 ± 2.18 µg protein/mL) unidentified biofilm bacterium EB4 [73]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB107 Actinobacteria Unidentified ND Xanthomonas campestris [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB132 Actinobacteria Unidentified ND X. campestris [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB138 Actinobacteria Unidentified ND X. campestris [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Unidentified ND X. campestris [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB253 Actinobacteria Unidentified ND X. campestris [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB291 Actinobacteria Unidentified ND X. campestris [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB298 Actinobacteria Unidentified ND X. campestris [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB132 Actinobacteria Unidentified ND Erwinia amylovora [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB202 Actinobacteria Unidentified ND E. amylovora [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB320 Actinobacteria Unidentified ND E. amylovora [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB328 Actinobacteria Unidentified ND E. amylovora [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB100 Actinobacteria Unidentified ND Ralstonia solanacearum [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB107 Actinobacteria Unidentified ND R. solanacearum [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB117 Actinobacteria Unidentified ND R. solanacearum [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB142 Actinobacteria Unidentified ND R. solanacearum [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB156 Actinobacteria Unidentified ND R. solanacearum [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB238 Actinobacteria Unidentified ND R. solanacearum [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB253 Actinobacteria Unidentified ND R. solanacearum [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB254 Actinobacteria Unidentified ND R. solanacearum [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB272 Actinobacteria Unidentified ND R. solanacearum [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB274 Actinobacteria Unidentified ND R. solanacearum [44]
Halichondria panicea Kiel Fjord, Baltic Sea, Germany (ND) Streptomyces sp. HB375 Actinobacteria Unidentified ND R. solanacearum [44]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. M101 Actinobacteria Unidentified DOI (>5 mm) unidentified marine bacterial isolate SW09 from sponge P. clavata (high G + C Gram-positive) [79]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. M102, M403, M413 Actinobacteria Unidentified DOI (>5 mm) unidentified marine bacterial isolate SW09 [79]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. M412 Actinobacteria Unidentified DOI (>5 mm) unidentified marine bacterial isolate SW09 [79]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. M414, SW10, SW 15 and SW 17 Actinobacteria Unidentified DOI (>5 mm) unidentified marine bacterial isolate SW09 [79]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. SW02 Actinobacteria Unidentified DOI (>5 mm) unidentified marine bacterial isolate SW09 [79]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. M101 Actinobacteria Unidentified DOI (>5 mm) unidentified marine bacterial isolate DE06 from sponge P. clavata: (low G + C Gram-positive) [79]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. M102, M403, M413 Actinobacteria Unidentified DOI (>5 mm) unidentified marine bacterial isolate DE06 [79]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. M412 Actinobacteria Unidentified DOI (>5 mm) unidentified marine bacterial isolate DE06 [79]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. SW02 Actinobacteria Unidentified DOI (>5 mm) unidentified marine bacterial isolate DE06 [79]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. M414, SW10, SW 15 and SW 17 Actinobacteria DOI (>5 mm) unidentified marine bacterial isolate DE06 [79]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. M101 Actinobacteria Unidentified DOI (>5 mm) unidentified bacterial isolate DE05 from sponge P. clavata (γ-proteobacteria) [79]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. M102, M403, M413 Actinobacteria Unidentified DOI (>5 mm) unidentified bacterial isolate DE05 (γ-proteobacteria) [79]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. M412 Actinobacteria Unidentified DOI (>5 mm) unidentified bacterial isolate DE05 (γ-proteobacteria) [79]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. M414, SW10, SW 15 and SW 17 Actinobacteria Unidentified DOI (>5 mm) Unidentified bacterial isolate DE05 (γ-proteobacteria) [79]
Pseudoceratina clavata Heron Island, Great Barrier Reef (14 m) Salinispora sp. SW02 Actinobacteria Unidentified DOI (>5 mm) Unidentified bacterial isolate DE05 (γ-proteobacteria) [79]

Table 2 is organised according to the target bacteria. IC50: half maximum inhibitory concentration; MIC: minimum inhibitory concentration; DOI: diameter of inhibition; ND: not determined. Susceptible to [77]: amp = ampicillin; atm = aztreonam; azm = azithromycin; caz = ceftazidimine; cef = cefalotin; chl = chloramphenicol; cip = ciprofloxacin; cpd = cefpodoxime; fox = cefoxitin; gen = gentamicin; oxa = oxacillin; pen = penicillin; sxt = trimethoprim/sulfamethoxazole; tet = tetracycline; tzp = piperacillin/tazobactam; van = vancomycin.

Figure 2.

Figure 2

Chemical structures of the antibacterial compounds YM-266183 (6), YM-266184 (7), kocurin (8), mayamycin (9), naphthacene glycoside SF2446A2 (10), sydonic acid (11) and trichoderin A (12).

Although many studies on antibacterial activity from sponge-associated microbes included Gram negative strains (Table 2), reports on pronounced antibacterial compounds active against Gram negative bacteria are limited in comparison to those that inhibit Gram positive strains. One of the examples of an inhibitor of a Gram negative bacterium is the compound naphthacene glycoside SF2446A2 (10) isolated from Streptomyces sp. RV15 that was originally obtained from the marine sponge Dysidea tupha [46]. Naphthacene glycoside SF2446A2 (10) inhibited the Gram-negative bacterium Chlamydia trachomatis at an IC50 value of 2.81 ± 0.24 µg/mL. Reimer et al. [46] underlined that compound 10 not only effectively inhibited the formation of chlamydial inclusion bodies during the primary infection but also affected the ability of C. trachomatis in producing viable progeny during the developmental cycle. Chlamydia trachomatis is an obligate intracellular Gram negative bacterium which is a leading cause of sexually transmitted diseases, and currently no methods are available to treat this infectious microorganism [46,47]. Li et al. [48] isolated four new bisabolane-typesesquiterpenoids: aspergiterpenoid A, (−)-sydonol, (−)-sydonic acid, (−)-5-(hydroxymethyl)-2-(2′,6′,6′-trimethyltetrahydro-2H-pyran-2-yl)phenol and a known compound (Z)-5-(Hydroxymethyl)-2-(6′-methylhept-2′-en-2′-yl)phenol from a sponge-associated Aspergillus sp. (Table 2). Of these five substances, the compound sydonic acid (11) exhibited the lowest MIC value against Escherichia coli at 1.33 µg/mL. This is the lowest inhibition concentration against E.coli reported from a compound produced by sponge-associated microbes although the inhibition concentration is still higher than the positive control ciprofloxacin (0.21 µg/mL) (Table 2).

Pruksakorn et al. [49] reported three prospective anti-tuberculosis compounds: trichoderin A (12), A1 and B from the sponge-associated fungus Trichoderma sp. 05FI48. Both under standard aerobic growth and dormancy-inducing hypoxic conditions, these three compounds inhibited Mycobacterium smegmatis, M. bovis BCG, and M. tuberculosis H37Rv with MIC values in the range of 0.02–2.0 µg/mL. Of these three compounds, trichoderin A was the most potent compound indicated by the lowest MIC values against those Mycobacterium strains. Additional analysis revealed that bioactivity of trichoderin A is based on its ability to inhibit adenosine triphosphate (ATP) synthesis of mycobacteria [50]. Compounds such as trichoderin A are particularly important because in many cases, pathogens such as Campylobacter spp., Helicobacter pylori, and Legionella pneumophila are difficult to treat due to the fact that they are present in a dormant state [51]. Such physiologically inactive cells highly contribute to the need for prolongued antibiotic treatments, which may lead to the emergence of resistant strains [52,53].

4. Antifungal Activity

The incidence rate of fungal infections has increased significantly over the past decades. This is mainly caused by clinical use of antibacterial drugs and immunosuppressive agents after organ transplantation, cancer chemotherapy, and advances in surgery [102,103]. Several fungal species that often cause human infections include Candida albicans, Candida glabrata, Cryptococcus neoformans and Aspergillus fumigatus [102,104,105]. The story becomes more complex as many of these pathogenic fungi develop resistance against available antifungal drugs, which will prolong duration of treatments [106].

Screening for antifungals is often focused on finding compounds active against Candida albicans, the prominent agent for candidiasis (Table 3). Invasive candidiasis is accounted as the most common nosocomial fungal infection resulting in an average mortality rate between 25%–38% [103]. El-Gendy et al. [107] isolated Streptomyces sp. Hedaya 48 from the sponge Aplysina fistularis and identified two compounds: the novel compound saadamycin (13) and the known compound 5,7-dimethoxy-4-p-methoxylphenylcoumarin (14) (Figure 3). Bioassays indicated that both saadamycin and 5,7-dimethoxy-4-p-methoxylphenylcoumarin displayed pronounced antifungal activity against Candida albicans with MIC values of 2.22 µg/mL and 15 µg/mL, respectively. In addition, both compounds displayed bioactivity against some pathogenic dermatophytes (skin-infecting fungi), such as Epidermophyton floccosum, Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum gypseum, Aspergillus niger, Aspergillus fumigatus, Fusarium oxysporum, and Cryptococcus humicolus (Table 3). Further analysis showed that saadamycin displayed a more potent bioactivity indicated by a 3875 fold lower MIC than that of the reference compound, miconazole, whereas 5,7-dimethoxy-4-p-methoxylphenylcoumarin was around a 200 fold more potent than miconazole.

Table 3.

Bioactive compounds with antifungal activity from sponge-associated microbes.

Sponge Origin (Depth) Microorganism Phylum Compound Property Target Reference
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria Saadamycin MIC (2.22 µg/mL) Candida albicans [107]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria 5,7-Dimethoxy-4-p-methoxylphenylcoumarin MIC (15 µg/mL) C. albicans [107]
Halichondria japonica Iriomote island, Japan (ND) Phoma sp. Q60596 Ascomycota YM-202204 IC80 (6.25 µg/mL) C. albicans [108]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Streptomyces sp. SM8 Actinobacteria Mixture of kitamycin A or B, and antimycin A3 or A7 MIC (240 µg/mL) C. albicans [95]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Streptomyces sp. SM8 Actinobacteria Antimycin A2, A8, A11, or A17 MIC (210 µg/mL) C. albicans [95]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Streptomyces sp. SM8 Actinobacteria Antimycin A3 or A7 MIC (80 µg/mL) C. albicans [95]
Haliclona simulans Gurraig Sound Kilkieran Bay, Ireland (15 m) Streptomyces sp. SM8 Actinobacteria Antimycin A2, A8, A11, or A17, antimycin A3 or A7 MIC (90 µg/mL) C. albicans [95]
Halichondria sp. West Coast of India (10 m) Bacillus sp. SAB1 Firmicutes 3-Phenylpropionic acid DOI (7–10 mm) at 50µg/disk C. albicans [69]
Halichondria sp. West Coast of India (10 m) Bacillus sp. SAB1 Firmicutes 4,4′-Oxybis(3-phenylpropionic acid) DOI (4–6 mm) at 50µg/disk C. albicans [69]
Xestospongia exigua Bali Sea, Indonesia (ND) Penicillium cf. montanense Ascomycota Xestodecalactone B MIC (28.03 µg/disk) C. albicans [111]
unidentified Iriomote island, Japan (ND) Streptomyces sp. Ni-80 Actinobacteria Urauchimycins A and B MIC (10 µg/mL) C. albicans [112]
Haliclona sp. Tateyama, Japan (ND) Streptomyces bambergiensis Actinobacteria Unidentified DOI (5 mm) C. albicans [113]
Haliclona sp. Tateyama, Japan (ND) Streptomyces javensis Actinobacteria Unidentified DOI (11 mm) C. albicans [113]
unidentified Nagura Bay, Ishigaki, Japan (ND) Streptomyces albidoflavus Actinobacteria Unidentified DOI (16 mm) C. albicans [113]
unidentified Nagura Bay, Ishigaki, Japan (ND) Streptomyces variabilis Actinobacteria Unidentified DOI (19 mm) C. albicans [113]
unidentified Nagura Bay, Ishigaki, Japan (ND) Streptomyces luteosporeus Actinobacteria Unidentified DOI (24 mm) C. albicans [113]
Spheciospongia vagabunda Rovinj, Croatia (3–20 m) Actinokineospora sp. EG49 Actinobacteria Unidentified DOI (12 mm) C. albicans [82]
Dysidea tupha Rovinj, Croatia (3–20 m) Streptomyces sp. RV15 Actinobacteria Unidentified DOI (4–6 mm) C. albicans [82]
Sigmadocia fibulatus Hare Island, India (5-10 m) Bacillus sp. SC3 Firmicutes Unidentified DOI (15 mm) C. albicans [96]
Sigmadocia fibulatus Hare Island, India (5-10 m) Pseudomonas sp. SC11 Proteobacteria Unidentified DOI (7 mm) C. albicans [96]
Echinodictyum sp. Hare Island, India (5-10 m) Idiomarina baltica SA7 Proteobacteria Unidentified DOI (10 mm) C. albicans [96]
Spongia sp. Hare Island, India (5-10 m) Staphylococcus equorum SB11 Firmicutes Unidentified DOI (10 mm) C. albicans [96]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A184 Firmicutes Surfactin, iturin, and fengycin ND C. albicans [68]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A190 Firmicutes Surfactin ND C. albicans [68]
Aplysina aerophoba Banyuls-sur-Mer, France (5–15 m) Bacillus subtilis A202 Firmicutes Iturin ND C. albicans [68]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Vibrio sp. SC-C1-5 Proteobacteria Unidentified ND C. albicans [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Vibrio sp. BSw21697 Proteobacteria Unidentified ND C. albicans [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Vibrio splendidus LGP32 Proteobacteria Unidentified ND C. albicans [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Bacillus amyloliquefaciens Proteobacteria Unidentified ND C. albicans [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Vibrio sp. SC-C1-5 Proteobacteria Unidentified ND Candida glabrata [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Vibrio sp. BSw21697 Proteobacteria Unidentified ND C. glabrata [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Vibrio splendidus LGP32 Proteobacteria Unidentified ND C. glabrata [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Bacillus amyloliquefaciens Firmicutes Unidentified ND C. glabrata [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Pseudoalteromonas sp. A2B10 Proteobacteria Unidentified ND C. glabrata [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Pseudoalteromonas sp. K2B-2 Proteobacteria Unidentified ND C. glabrata [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Pseudoalteromonas sp. LJ1 Proteobacteria Unidentified ND C. glabrata [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Pseudoalteromonas sp. S3178 Proteobacteria Unidentified ND C. glabrata [83]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria Saadamycin MIC (5 µg/mL) Trichophyton rubrum [107]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria 5,7-Dimethoxy-4-p-methoxylphenylcoumarin MIC (7.5 µg/mL) T. rubrum [107]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria Saadamycin MIC (1.5 µg/mL) Trichophyton mentagrophytes [107]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria 5,7-Dimethoxy-4-p-methoxylphenylcoumarin MIC (90 µg/mL), T. mentagrophytes [107]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria Saadamycin MIC (1.25 µg/mL) Microsporum gypseum [107]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria 5,7-Dimethoxy-4-p-methoxylphenylcoumarin MIC (100 µg/mL) M. gypseum [107]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria Saadamycin MIC (1.0 µg/mL) Epidermophyton floccosum [107]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria 5,7-Dimethoxy-4-p-methoxylphenylcoumarin MIC (50 µg/mL) E. floccosum [107]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria Saadamycin MIC (1.2 µg/mL) Fusarium oxysporum [107]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria 5,7-Dimethoxy-4-p-methoxylphenylcoumarin MIC (22 µg/mL) F. oxysporum [107]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria Saadamycin MIC (5.16 µg/mL) Cryptococcus humicolus [107]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria 5,7-Dimethoxy-4-p-methoxylphenylcoumarin MIC (10 µg/mL) C. humicolus [107]
Halichondria japonica Iriomote island, Japan (ND) Phoma sp. Q60596 Ascomycota YM-202204 IC80 (1.56 µg/mL) Cryptococcus neoformans [108]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria Saadamycin MIC (1.6 µg/mL) Aspergillus fumigatus [107]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria 5,7-Dimethoxy-4-p-methoxylphenyl-coumarin MIC (10 µg/mL) A. fumigatus [107]
Halichondria japonica Iriomote island, Japan (ND) Phoma sp. Q60596 Ascomycota YM-202204 IC80 (12.5 µg/mL) A. fumigatus [108]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Staphylococcus saprophyticus Firmicutes Unidentified ND A. fumigatus [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Staphylococcus sp. HJB003 Firmicutes Unidentified ND A. fumigatus [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Vibrio litoralis MANO22P Proteobacteria Unidentified ND A. fumigatus [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Vibrio sp. SC-C1-5 Proteobacteria Unidentified ND A. fumigatus [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Vibrio sp. BSw21697 Proteobacteria Unidentified ND A. fumigatus [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Vibrio splendidus LGP32 Proteobacteria Unidentified ND A. fumigatus [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Bacillus amyloliquefaciens Firmicutes Unidentified ND A. fumigatus [83]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria Saadamycin MIC (1.0 µg/mL) Aspergillus niger [107]
Aplysina fistularis Sharm El-Sheikh, Egypt (ND) Streptomyces sp. Hedaya48 Actinobacteria 5,7-Dimethoxy-4-p-methoxylphenylcoumarin MIC (20 µg/mL) A. niger [107]
Halichondria sp. West Coast of India (10 m) Bacillus sp. SAB1 Firmicutes 3-Phenylpropionic acid DOI (1–3 mm) at 50 µg/disc A. niger [69]
Halichondria sp. West Coast of India (10 m) Bacillus sp. SAB1 Firmicutes 4,4′-Oxybis(3-phenylpropionic acid) DOI (4–6 mm) at 50 µg/disc A. niger [69]
Halichondria sp. West Coast of India (10 m) Bacillus sp. SAB1 Firmicutes 3-Phenylpropionic acid DOI (4–6 mm) at 50 µg/disc Rhodotorula sp. [69]
Halichondria sp. West Coast of India (10 m) Bacillus sp. SAB1 Firmicutes 4,4′-Oxybis(3-phenylpropionic acid) DOI (7–10 mm) at 50 µg/disc Rhodotorula sp. [69]
Halichondria japonica Iriomote island, Japan (ND) Phoma sp. Q60596 Ascomycota YM-202204 IC80 (1.56 µg/mL) Saccharomyces cerevisiae [108]
Hymeniacidon perleve Nanji island, China (ND) Pseudoalteromonas piscicida NJ6-3-1 Proteobacteria Norharman (a beta-carboline alkaloid) DOI (3–5 mm) S. cerevisiae [59]
Hymeniacidon perleve Nanji island, China (ND) Bacillus megaterium NJ6-3-2 Firmicutes Unidentified DOI (3–5 mm) S. cerevisiae [59]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Vibrio litoralis MANO22P Proteobacteria Unidentified ND S. cerevisiae [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Vibrio sp. SC-C1-5 Proteobacteria Unidentified ND S. cerevisiae [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Vibrio sp. BSw21697 Proteobacteria Unidentified ND S. cerevisiae [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Vibrio splendidus LGP32 Proteobacteria Unidentified ND S. cerevisiae [83]
Leucosolenia sp. Lough Hyne, Co. Cork, Ireland (15 m) Bacillus amyloliquefaciens Firmicutes Unidentified ND S. cerevisiae [83]
Psammocinia sp. Sdot-Yam, Israel (ND) Aspergillus insuetus Ascomycota Insuetolides A MIC (60.09 µg/mL) Neurospora crassa [114]
Psammocinia sp. Sdot-Yam, Israel (ND) Aspergillus insuetus Ascomycota Strobilactone A MIC (69.97 µg/mL) N. crassa [114]
Psammocinia sp. Sdot-Yam, Israel (ND) Aspergillus insuetus Ascomycota (E,E)-6-(60,70-Dihydroxy-20,40-octadienoyl)-strobilactone A MIC (71.79 µg/mL) N. crassa [114]
Myxilla incrustans The Caribbean Island of Dominica (ND) Microsphaeropsis sp. Ascomycota Microsphaeropsisin ND Eurotium repens [115]
Myxilla incrustans The Caribbean Island of Dominica (ND) Microsphaeropsis sp. Ascomycota (R)-Mellein ND E. repens [115]
Myxilla incrustans The Caribbean Island of Dominica (ND) Microsphaeropsis sp. Ascomycota (3R,4R)-Hydroxymellein ND E. repens [115]
Myxilla incrustans The Caribbean Island of Dominica (ND) Microsphaeropsis sp. Ascomycota 4,8-Dihydroxy-3,4-dihydro-2H-naphthalen-1-one ND E. repens [115]
Ectyoplasia ferox The Caribbean Island of Dominica (ND) Coniothyrium sp. Ascomycota (3R)-6-Methoxymellein ND E. repens [115]
Ectyoplasia ferox The Caribbean Island of Dominica (ND) Coniothyrium sp. Ascomycota (3R)-6-Methoxy-7-chloromellein ND E. repens [115]
Ectyoplasia ferox The Caribbean Island of Dominica (ND) Coniothyrium sp. Ascomycota (p-Hydroxyphenyl) ethanol ND E. repens [115]
Ectyoplasia ferox The Caribbean Island of Dominica (ND) Coniothyrium sp. Ascomycota Phenylethanol ND E. repens [115]
Myxilla incrustans The Caribbean Island of Dominica (ND) Microsphaeropsis sp. Ascomycota Microsphaeropsisin ND Ustilago violacea [115]
Myxilla incrustans The Caribbean Island of Dominica (ND) Microsphaeropsis sp. Ascomycota (R)-Mellein ND U. violacea [115]
Myxilla incrustans The Caribbean Island of Dominica (ND) Microsphaeropsis sp. Ascomycota (3R,4R)-Hydroxymellein ND U. violacea [115]
Myxilla incrustans The Caribbean Island of Dominica (ND) Microsphaeropsis sp. Ascomycota 4,8-Dihydroxy-3,4-dihydro-2H-naphthalen-1-one ND U. violacea [115]
Ectyoplasia ferox The Caribbean Island of Dominica (ND) Coniothyrium sp. Ascomycota (3R)-6-Methoxymellein ND U. violacea [115]
Ectyoplasia ferox The Caribbean Island of Dominica (ND) Coniothyrium sp. Ascomycota (3R)-6-Methoxy-7-chloromellein ND U. violacea [115]
Ectyoplasia ferox The Caribbean Island of Dominica (ND) Coniothyrium sp. Ascomycota (p-Hydroxyphenyl) ethanol ND U. violacea [115]
Ectyoplasia ferox The Caribbean Island of Dominica (ND) Coniothyrium sp. Ascomycota Phenylethanol ND U. violacea [115]
Ectyoplasia ferox The Caribbean Island of Dominica (ND) Coniothyrium sp. Ascomycota (3S)-(3’,5’-Dihydroxyphenyl)butan-2-one ND U. violacea [115]
Ectyoplasia ferox The Caribbean Island of Dominica (ND) Coniothyrium sp. Ascomycota (3S)-(3’,5’-Dihydroxyphenyl)butan-2-one ND Mycotypha microspora [115]

Table 3 is organised according to the target fungi. IC50: half maximum inhibitory concentration; IC80: 80% inhibitory concentration; MIC: minimum inhibitory concentration; DOI: diameter of inhibition; ND: not determined.

Figure 3.

Figure 3

Chemical structures of the antifungal compounds saadamycin (13), 5,7-dimethoxy-4-p-methoxylphenylcoumarin (14) and YM-202204 (15).

Antifungal activity was also detected from the sponge-associated fungus Phoma sp. Q60596. The sponge-derived fungus produced a new lactone compound, YM-202204 (15) [108], which was effective against C. albicans (IC80 of 6.25 µg/mL), along with Cryptococcus neoformans (IC80 of 1.56 µg/mL), Saccharomyces cerevisiae (IC80 of 1.56 µg/mL) and Aspergillus fumigatus (IC80 of 12.5 µg/mL). Furthermore, Nagai et al. [108] showed that YM-202204 was able to block the glycophosphatidylinositol (GPI) anchor, an important structure for protein attachment in the membrane of eukaryotic cells and one of the targets in developing antifungal drugs [109,110].

5. Antiprotozoal Activity

Malaria, caused by Plasmodium spp. infections, represents the most devastating protozoal disease worldwide, and results in both mortality and economic loss, mainly in developing countries [116]. Developing drugs with a better therapeutic profile against the parasite is one of the key aims of current malaria research, which includes screening for antimalarial substances from marine organisms [117,118].

Manzamine A (16) (Figure 4), first reported by Sakai and co-workers [119] from the sponge Haliclona sp., is a promising substance against Plasmodium spp. Initially, its antitumor property was of main interest, but subsequently diverse antimicrobial activities such as: anti-HIV, antibacterial, and antifungal were identified from the compound [120]. Currently the antimalaria properties of manzamine A are considered its most promising bioactivity. Manzamine A was shown to inhibit P. falciparum D6 and W3 clonal cell lines that are sensitive and resistant against the antimalarial chloroquine [121], with IC50 values of 0.0045 and 0.008 µg/mL, respectively [122]. Furthermore, in vivo screening by Ang et al. [116] showed that manzamine A at concentration of 0.008 µg/mL inhibited 90% growth of the parasite Plasmodium berghei that causes malaria in rodents. In addition, Rao et al. reported [122] that manzamine A displayed anti-Leishmania activity, indicated by IC50 and IC90 values of 0.9 µg/mL and 1.8 µg/mL, respectively, against Leishmania donovani.

Figure 4.

Figure 4

Chemical structures of the antiprotozoal compounds manzamine A (16), valinomycin (17), staurosporine (18) and butenolide (19).

Isolation of manzamine A from several other sponge species [120] raised the hypothesis that it was of microbial origin [123,124]. Hill et al. [125] confirmed this hypothesis by isolating Micromonospora sp. M42 as the microbial producer of manzamine A from the Indonesian sponge Acanthostrongylophora ingens. A series of analyses using molecular-microbial community analysis, and Matrix Assisted Laser Desorption Ionization-Mass Spectrometry (MALDI-MS) corroborated that indeed the strain Micromonospora sp. M42 synthesizes manzamine A [126,127]. Considering the therapeutic potential of manzamine A for treating malaria and leishmaniasis, Micromonospora sp. M42 could be a sustainable provider of the substance, because the “Sponge Supply Problem” has been overcome [127]. Moreover, identification of several manzamine-derivatives e.g. manzamine E, F, J, and 8-hydroxymanzamine A, from marine sponges which displayed antibacterial, antifungal and antiprotozoal activity [122,124], could also lead to isolation of associated microbial producers in the future.

Pimentel-Elardo et al. [128] identified three compounds with anti-Leishmania and anti-Trypanosoma activity from a sponge-associated Streptomyces sp, namely the cyclic depsipeptide valinomycin (17), the indolocarbazole alkaloid staurosporine (18) and butenolide (19) (Table 4). Valinomycin and staurosporine inhibited the growth of L. major with IC50 values of 0.12 µg/mL and 1.24 µg/mL, respectively. In addition, the three compounds displayed bioactivity against Trypanosoma brucei with IC50 values of 0.0036 µg/mL for valinomycin, 0.0051 µg/mL for staurosporine and 7.92 µg/mL for butenolide.

Table 4.

Bioactive compounds with antiprotozoal activity from sponge-associated microbes.

Sponge Origin (Depth) Microorganism Phylum Compound Property Target References
Homophymia sp. Touho, New Caledonia (ND) Pseudomonas sp. 1531-E7 Proteobacteria 2-Undecyl-4-quinolone IC50 (1 μg/mL) Plasmodium falciparum [25]
Acanthostrongylophora ingens Manado, Indonesia (ND) Micromonospora sp. M42 Actinobacteria Manzamine A IC50 (0.0045 µg/mL) P. falciparum [124,125,126,127]
Hyattella intestinalis Palk strait, Tamil Nadu, India (ND) unidentified bacterial isolate THB20 Unidentified Unidentified IC50 (41.88 µg/mL) P. falciparum [131]
Stylissa carteri Palk strait, Tamil Nadu, India (ND) unidentified bacterial isolate THB17 Unidentified Unidentified IC50 (20.56 µg/mL) P. falciparum [132]
Clathria indica Palk strait, Tamil Nadu, India (ND) unidentified bacterial isolate THB23 Unidentified Unidentified IC50 (28.80 µg/mL) P. falciparum [133]
Clathria vulpina Palk strait, Tamil Nadu, India (ND) unidentified bacterial isolate THB15 Unidentified Unidentified IC50 (20.73 µg/mL) P. faciparum [134]
Haliclona grant Palk strait, Tamil Nadu, India (ND) unidentified bacterial isolate THB14 Unidentified Unidentified IC50 (11.98 µg/mL) P. faciparum [135]
Acanthostrongylophora ingens Manado, Indonesia (ND) Micromonospora sp. M42 Actinobacteria Manzamine A In vivo inhibition (90%) at concentration of 0.008 µg/mL Plasmodium berghei [116,125,126,127]
Aplysina aerophoba Rovinj, Croatia (3–20 m) Micromonospora sp. RV115 Actinobacteria Diazepinomicin IC50 (6.29 µg/mL) Trypanosoma brucei [136]
Spheciospongia vagabunda Rovinj, Croatia (3–20 m) Actinokineospora sp. EG49 Actinobacteria Unidentified Percentage of growth inhibition (48%) T. brucei [82]
unidentified Rovinj, Croatia (3–20 m) Brevibacterium sp. EG10 Actinobacteria Unidentified Percentage of growth inhibition growth inhibition (30%) T. brucei [82]
unidentified Rovinj, Croatia (3–20 m) Gordonia sp. EG50 Actinobacteria Unidentified Percentage of growth inhibition growth inhibition (28%) T. brucei [82]
Dysidea tupha Rovinj, Croatia (3–20 m) Kocuria sp. RV89 Actinobacteria Unidentified Percentage of growth inhibition growth inhibition (19%) T. brucei [82]
Dysidea avara Mediterranean sea (ND) Nocardiopsis sp. RV163 Actinobacteria 1,6-Dihydroxyphenazine (produced from co-culture) IC50 (4.03 µg/mL) T. brucei [98]
Spheciospongia vagabunda Red Sea (ND) Actinokinespora sp. EG49 Actinobacteria Actinosporin A IC50 (19.19 µg/mL) T. brucei brucei [137]
Aplysina polypoides Rovinj, Croatia (3–20 m) Streptomyces sp. 34 Actinobacteria Valinomycin IC50 (0.0036 µg/mL) T. brucei brucei [128]
Axinella aerophoba Rovinj, Croatia (3–20 m) Streptomyces sp. 22 Actinobacteria Valinomycin IC50 (0.0036 µg/mL) T. brucei brucei [128]
Tedania sp. Rovinj, Croatia (3–20 m) Streptomyces sp. 11 Actinobacteria Staurosporine IC50 (0.0051 µg/mL) T. brucei brucei [128]
Tethya sp. Rovinj, Croatia (3–20 m) Streptomyces sp. T03 Actinobacteria Butenolide IC50 (7.92 µg/mL) T. brucei brucei [128]
Petrosia ficiformis Milos, Greece (ND) Streptomyces sp. SBT344 Actinobacteria Unidentified IC50 (<10 µg/mL) T. brucei brucei [138]
Sarcotragus foetidus Milos, Greece (ND) Modestobacter sp. SBT363 Actinobacteria Unidentified IC50 (<10 µg/mL) T. brucei brucei [138]
Sarcotragus foetidus Milos, Greece (ND) Nonomuraea sp. SBT364 Actinobacteria Unidentified IC50 (<10 µg/mL) T. brucei brucei [138]
Phorbas tenacior Crete, Greece (ND) Micromonospora sp. SBT687 Actinobacteria Unidentified IC50 (14.87 µg/mL) T. brucei brucei [138]
Petrosia ficiformis Milos, Greece (ND) Streptomyces sp. SBT348 Actinobacteria Unidentified IC50 (16.52 µg/mL) T. brucei brucei [138]
Ircinia variabilis Milos, Greece (ND) Geodermatophilus sp. SBT381 Actinobacteria Unidentified IC50 (18.60 µg/mL) T. brucei brucei [138]
Spirastrella cunctatrix Milos, Greece (ND) Modestobacter sp. SBT362 Actinobacteria Unidentified IC50 (19.34 µg/mL) T. brucei brucei [138]
Spirastrella cunctatrix Milos, Greece (ND) Rhodococcus sp. SBT367 Actinobacteria Unidentified IC50 (19.97 µg/mL) T. brucei brucei [138]
Axinella polypoides Banyuls-sur-Mer, France (ND) Streptomyces axinellae Pol001T Actinobacteria Tetromycin 1 IC50 (26.02 µg/mL) T. brucei brucei [139]
Axinella polypoides Banyuls-sur-Mer, France (ND) Streptomyces axinellae Pol001T Actinobacteria Tetromycin 2 IC50 (40.35 µg/mL) T. brucei brucei [139]
Axinella polypoides Banyuls-sur-Mer, France (ND) Streptomyces axinellae Pol001T Actinobacteria Tetromycin 3 IC50 (23.18 µg/mL) T. brucei brucei [139]
Axinella polypoides Banyuls-sur-Mer, France (ND) Streptomyces axinellae Pol001T Actinobacteria Tetromycin 4 IC50 (32.17 µg/mL) T. brucei brucei [139]
Axinella polypoides Banyuls-sur-Mer, France (ND) Streptomyces axinellae Pol001T Actinobacteria Tetromycin B IC50 (17.20 µg/mL) T. brucei brucei [139]
Aplysina polypoides Rovinj, Croatia (3–20 m) Streptomyces sp. 34 Actinobacteria Valinomycin IC50 (<0.12 µg/mL) Leishmania major [128]
Axinella aerophoba Rovinj, Croatia (3–20 m) Streptomyces sp. 22 Actinobacteria Valinomycin IC50 (<0.12 µg/mL) L. major [128]
Tedania sp. Rovinj, Croatia (3–20 m) Streptomyces sp. 11 Actinobacteria Staurosporine IC50 (1.24 µg/mL) L. major [128]
Axinella polypoides Banyuls-sur-Mer, France (ND) Streptomyces axinellae Pol001T Actinobacteria Tetromycin 3 IC50 (31.72 µg/mL) L. major [139]
Spheciospongia vagabunda Rovinj, Croatia (3–20 m) Actinokineospora sp. EG49 Actinobacteria Unidentified growth inhibition (48%) L. major [82]
unidentified Rovinj, Croatia (3–20 m) Gordonia sp. EG50 Actinobacteria Unidentified growth inhibition (28%) L. major [82]
Axinella corrugata The Arvoredo Biological Marine Reserve, Brazil (ND) Hypocrea lixii F02 Ascomycota Unidentified MIC (250 µg/mL) Trichomonas vaginalis ATCC 30236 [129]
Axinella corrugata The Arvoredo Biological Marine Reserve, Brazil (ND) Hypocrea lixii F02 Ascomycota Unidentified MIC (250 µg/mL) T. vaginalis fresh isolate [129]
Axinella corrugata The Arvoredo Biological Marine Reserve, Brazil (ND) Hypocrea lixii F02 Ascomycota Unidentified MIC (250 µg/mL) T. vaginalis metronidazole-resistant LACM2 [129]
Stoeba sp. The Arvoredo Biological Marine Reserve, Brazil (ND) Penicillium citrinum F40 Ascomycota Unidentified MIC (250 µg/mL) T. vaginalis ATCC 30236 [129]
Stoeba sp. The Arvoredo Biological Marine Reserve, Brazil (ND) Penicillium citrinum F40 Ascomycota Unidentified MIC (250 µg/mL) T. vaginalis fresh isolate [129]
Stoeba sp. The Arvoredo Biological Marine Reserve, Brazil (ND) Penicillium citrinum F40 Ascomycota Unidentified MIC (250 µg/mL) T.vaginalis metronidazole-resistant LACM2 [129]

Table 4 is organised according to the target protozoa. IC50: half maximum inhibitory concentrations; MIC: minimum inhibitory concentration; ND: not determined.

Scopel et al. [129] isolated two sponge-associated fungi, namely Hypocrea lixii F02 and Penicillium citrinum F40 (Table 4) that were active against the protozoal parasite Trichomonas vaginalis, which causes trichomoniasis, a sexually transmitted disease [130]. Culture filtrates of both isolates inhibited T. vaginalis ATCC 30236 and fresh clinical isolates, including the metronidazole-resistant TV-LACM2, with MIC values of 2.5 mg/mL. Further observation indicated that culture filtrates of these two fungi had no haemolytic effect against mammalian cells, which is one of the important criteria to further develop anti-protozoal drugs [129].

6. Dicussion

6.1. Antimicrobial Compounds from Sponge-Associated Microbes: What We Learned So Far

Bioprospecting is the effort to discover natural compounds with therapeutic and biological applications [140]. In line with this definition, sponge-associated microbes offer a huge potential as the source of antimicrobial substances as shown by many microbial isolates being reported to inhibit pathogenic reference strains in vitro and to synthesize active substances against one or several groups of infectious agents. Based on our review, antimicrobial compounds produced by sponge-associated microbes with the most pronounced bioactivity include: 2-undecyl-4-quinolone, sorbicillactone A, stachybotrin D and chartarutine B against HIV-1; truncateol M against H1N1 M; YM-266183, YM-266184, kocurin, mayamycin, sydonic acid, naphthacene glycoside SF2446A2 and trichoderin A against a variety of bacterial strains; saadamycin and YM-202204 against fungi; manzamine-A against malaria; and valinomycin against Trypanosoma. In this case the most pronounced activity is solely based on reported inhibition data and does not yet take potential side effects into account. Therefore the most promising compounds may be ones that have higher IC50 values, but cause less side effects. As these data are not available for the majority of the reported compounds, we have focused on the most potent compounds.

Sponge-associated bacteria and fungi are the two groups of microorganisms that have been found to produce antimicrobial compounds (Figure 5). The large majority of the antimicrobial compounds found in sponge-associated microbiota is produced by bacteria (90%), while fungi account for approximately 10% of the compounds reported. Sponge-associated bacteria derived antimicrobial compounds were found from 35 genera (Figure 5B). At a higher taxonomic level, these 35 bacterial genera can be classified into the four phyla Actinobacteria, Proteobacteria, Firmicutes and Cyanobacteria with percentages of 48.8%, 36.6%, 11.4% and 0.4% respectively. In contrast, sponge-associated fungi that have been found to produce antimicrobials are affiliated solely to the phylum Ascomycota.

Figure 5.

Figure 5

Distribution of sponge-associated microorganisms found to produce antimicrobial compounds: (A) Bacteria and Fungi; (B) Bacterial genera; and (C) Fungal genera. Figure 5 was made based on the summary of the taxonomic affiliations of sponge-associated microbes (N = 272) that were found to produce antimicrobials.

Streptomyces is the most prominent genus as indicated by 30% of sponge bacteria-derived compounds. Streptomyces has become a main target for screening for bioactive compounds both from terrestrial and marine environments due to the high diversity of secondary metabolites they produce [141,142]. Of the many sponge-associated Streptomyces isolates reported, Streptomyces sp. HB202 and Streptomyces sp. RV15 are of particular interest in term of producing antibacterial compounds. Streptomyces sp. HB202, isolated from the sponge Halichondria panicea has been documented to produce three antibacterial substances: mayamycin, streptophenazine G and K, which are mainly active against Gram positive pathogenic bacteria (Table 2). Streptomyces sp. RV15, on the other hand, produces the compound naphthacene glycoside which up to now is the only anti-Chlamydia reported from sponge-associated microbes [46]. In addition, the report on crude extract inhibition of Streptomyces sp. RV15 against S. aureus and E. faecalis [82] may give a hint to discover other antibacterial substances from this strain. Streptomyces sp. Hedaya48 is currently the most potent sponge-associated bacterial isolate for antifungal activities with the production of saadamycin and 5,7-dimethoxy-4-p-methoxylphenylcoumarin [107]. In addition, isolation of the anti-Trypanosoma and anti-Leishmania compounds valinomycin, staurosporine and butenolide from Streptomyces sp. 43, 21 and 11 [128], affirms Streptomyces as the currently most prominent producer of antimicrobial substances from sponges.

Pseudovibrio follows as the second most prolific bacterial genus isolated from sponges (20%) with respect to antimicrobial activities. Reports on Pseudovibrio spp. are concentrated on antibacterial activity and are mainly based on screening of crude extracts. Up to now, tropodithietic acid is the only antibacterial compound that has been identified from Pseudovibrio [72]. Although representing a lower percentage of the sponge-associated bacteria found to produce antimicrobials than Streptomyces and Pseudovibrio, 9% of the currently known bioactives was found to be produced by sponge-associated Bacillus spp., with activities against viruses, bacteria and fungi. Bacillus cereus QNO3323 is currently the most prominent antimicrobial producer from this genus with the very potent thiopeptides YM-266183 and YM-266184 that are active against Gram positive bacteria.

Sponge-associated Ascomycota found to produce antimicrobials can be further classified into 12 genera. Of these 12 fungal genera, Aspergillus (30%) and Penicillium (23%) are currently the two most prominent groups of sponge-associated fungi reported as antimicrobial producers. This finding is not suprising since both Aspergillus and Penicillium are known prolific producers of secondary metabolites from other sources [143]. Aspergillus versicolor [58] and an unidentified Aspergillus sp. isolated from the sponge Xestospongia testudinaria [48] showed a strong antibacterial activity as indicated by potent inhibition of pathogenic bacteria. The antimicrobial activities found from sponge-associated Penicillium spp. are particular remarkable as it is the only fungal genus that is found to produce antivirals, antibacterials antifungals and antiprotozoals. Penicillium chrysogenum [26] and Penicillium sp. FF01 [57] are to date the most promising sponge-associated Penicillium isolates for which anti-HIV activity (sorbicillactone) and antibacterial activity (citrinin) were reported, respectively. Sponge-derived Stachybotrys spp. are only known for antiviral activity, particularly against HIV and enterovirus 71 (EV71), and there are no reports of other antimicrobial activities. Generally, although the number of produced antimicrobials is outnumbered by those of sponge-associated bacteria, sponge-associated fungi should be considered as an important reservoir of antimicrobial compounds.

When the chemical structures of sponge-microbe-derived compounds are considered, a rather diverse array of structures is observed, including peptides, terpenoids, phenazines, indoles, phenoles and polyketides. Sixty percent of the antivirals from sponge-associated microbes are ketone derivatives (quinolone, sorbicillactone, isoindolinone, butyrolactone, furanone, xanthone, methanone, phenone). Peptide derivatives constitute 19% of the total identified antibacterial substances and roughly 12.5% from the total antimicrobial compounds reviewed here. Phenazine derivatives are the second most frequently isolated class of antibacterial compounds from sponge-associated microbes (15%) as exemplified in this review by the antibacterial compounds streptophenazine [89], phenazine alkaloid antibiotics [55], 6-hydroxymethyl-1-phenazine-carboxamide and 1,6-phenazinedimethanol [94]. Phenazine is a nitrogen-containing heterocyclic compound with a wide range of biological activities [67,144], and several studies from terrestrial environments and chemically synthesized phenazines have been reported as antiviral [145], antibacterial [146], and antimalaria [147]. Moreover, this group of compounds is attractive for therapeutic application since their structures are relatively small and hence can easily reach tissues and organs [67,148].

6.2. Discovering Antimicrobial Compounds from Sponge-Associated Microbes: From Culture-Dependent to Culture-Independent Methods

Isolation of antimicrobial producers provides a valuable basis for assessing the biotechnological potential of sponge-associated microbes. In a wider perspective, however, only a small fraction of this sponge-microbial community has been isolated under laboratory conditions leaving the majority resistant to in vitro growth with current cultivation approaches [15,149,150]. Several studies have focused on improving cultivability of sponge-associated microbes. Some of the approaches include using low nutrient media [151], floating filter cultures [152], employing different carbon sources, e.g., lectin [153], sponge extracts [152], and in situ cultivation using a diffusion growth chamber [154]. Furthermore, flow-cytometry and density gradient centrifugation have been applied to separate sponge cells from their associated bacteria to enrich the inoculum [155,156]. Additionally, co-cultivation through mixing of two or more microbial isolates in vitro [157] is an approach proposed to discover more natural compounds from sponge-associated microbes. The idea behind co-culture lies in the fact that many biosynthetic gene clusters found in microorganisms remain cryptic under standard laboratory conditions, and co-cultivation might provide a possibility to activate these silent genes [158,159]. As an example, the co-culture by Dashti et al. [98] of the sponge-associated Actinobacteria, Actinokinespora sp. EG49 and Nocardiopsis sp. RV163, resulted in isolation of the antibacterial compound 1,6-dihydroxyphenazine, which was not found from the individual isolates. However, even if the cultivability of sponge-associated microbes is improved, there is a long way ahead to reach a point that we will be able to isolate and routinely cultivate 50% of the microbes that are found in sponges. At the same time, the advance of genetic and molecular studies has resulted in the development of tools to study genes, transcripts and proteins by directly analyzing environmental DNA, RNA and proteins, thus bypassing cultivation procedures [157]. In relation to screening for antimicrobial activity, metagenomics has been applied to identify antimicrobials of uncultivated microorganisms from terrestrial environments, such as the antimycobacterial nocardamine, the putative antibacterial activity of terragines A–E [160], violacein that is active against S. aureus, Bacillus sp. and Streptococcus sp. [161] and a polyketide with activity against the yeast Saccharomyces cerevisiae [162].

Two main metagenomic approaches, functional screening and sequence homology-based methods, are generally distinguished [163]. Functional screening relies on detection of the metabolic activities of metagenomic library clones without requiring any prior sequence information [163,164,165]. Gillespie et al. [9] applied function-based metagenomics with E. coli as expression host, to identify the antibiotics turbomycin A and B from a soil sample. MacNeil et al. [166] identified the antimicrobial indirubin by constructing a BAC (bacterial artificial chromosome) library in E.coli. Yung et al. [167] reported two hydrolytic enzymes from fosmid clones CcAb1 and CcAb2, which were derived from a metagenome of the sponge Cymbastela concentrica using E. coli as the host. Both fosmid clones inhibited the growth of Bacillus sp. with an inhibition diameter of 20 mm, and clone CcAb1 showed additional inhibition of S. aureus and an Alteromonas sp. with diameters of inhibition of 50 mm and 60 mm, respectively. Further phylogenetic analysis showed that active genes encoding for these enzymes were of microbial origin [167]. He et al. [168] constructed a fosmid library of the sponge Discodermia calyx using E. coli as the host and identified antimicrobial activity of the enzyme 3-hydroxypalmitic acid against B. cereus and C. albicans. In addition, using the same approach He et al. [169] observed an active clone, pDC113, that displayed a clear inhibition zone against B. cereus. Subsequently, 11 cyclodipeptides were identified from this clone. Generally, it can be stated that although a number of antimicrobials have been discovered through functional screening of metagenomic libraries from sponges, the expression of large gene clusters such as those encoding (polyketide synthase( PKS) and (non-ribosomal peptide synthetase (NRPS) is still a difficult hurdle to take. Several key elements need to be considered to achieve successful expression of biosynthetic gene clusters; namely mobilizing the biosynthetic pathway into a suitable vector, selecting an appropriate heterologous host and stably maintaining the gene clusters in the host [170]. The size of many of these gene clusters requires the use of cloning vectors that can accept large inserts, such as fosmids, or BACs if the required insert size is over 100 kb [171]. Selection of heterologous expression systems in particular is a crucial factor before applying functional metagenomics to identify antimicrobials, because expression hosts are microbes as well and especially clones that express genes encoding for enzymes involved in production of antimicrobials may therefore be non-viable. Ongley et al. [170] pointed out some considerations in selecting an expression host such as relatedness to the native producer, availability of genetic tools and precursors, a high growth rate, and suitability for fermentation at a large scale. E. coli, the most commonly used expression host, has limitations for expressing parts of metagenomes because, e.g., of the sheer size of some gene clusters, genes with deviating codon usage, incompatible regulatory elements, lack of biosynthesis precursors or unavailability of posttranslational modifications [165,172]. Therefore, in order to make screening for antimicrobials through metagenomic libraries more efficient, it is of utmost importance to diversify the suite of expression hosts used. Several non-E.coli hosts, such as Agrobacterium tumefaciens, Bacillus subtilis, Burkholderia graminis, Caulobacter vibrioides, Pseudoalteromonas haloplanktis, Pseudomonas putida, Ralstonia metallidurans, Rhizobium leguminosarum, Streptomyces avermitilis, S. albus, Pseudomonas putida, Sulfolobus solfataricus, Thermus thermophilus, Thiocapsa roseopersicina and Saccharopolyspora sp. have been developed and should be more seriously considered as expression hosts when performing metagenomic screenings for antimicrobials [165,172,173].

Sequence-based screening, on the other hand, requires information on the sequence of genes involved in the production of a natural product as guidance to search for similar sequences in a sequenced metagenomic library or scaffolds reconstructed from direct metagenomic sequencing [165]. Homology-based screening is suitable to identify a compound with highly conserved biosynthesis pathways, e.g., those mediated by PKS and NRPS [174]. Piel and colleagues [175,176,177,178,179] applied this method, and identified the antitumor polyketide onnamide from uncultivated bacteria of the sponge T. swinhoei. Sequence-based screening was applied by Fisch [180] to unravel the complete pathway of the polyketide psymberin that was found to possess a potent antitumor activity, from uncultivated sponge-associated microbes. By sequence-based screening of metagenomic libraries, Schirmer et al. [181] reported diverse polyketide gene clusters in microorganisms from the sponge Discodermia dissoluta. The development of techniques that yield longer read lengths, such as Pacific Biosciences (PacBio) RS II SMRT (Single Molecule Real-Time) sequencing technology, in which a single read can be extended over 10 kbp [182], can be instrumental in increasing the accuracy in assembling large gene clusters. Application of PacBio for secondary metabolite gene clusters has been reported by Alt and Wilkinson [183], who identified the 53,253 bp genomic fragment encoding the transacyltransferase (trans-AT) polyketide synthase (PKS) from a marine Streptomyces sp responsible for the production of the antibiotic anthracimycin (atc). Furthermore, using Streptomyces coelicolor as heterologous expression host, the authors confirmed production of anthracimycin [183]. Furthermore, single cell analysis by combining cell separation and fluorescence-assisted cell sorting (FACS) could be a strategy to overcome the complexity of the microbial community in sponges since this method can be used to select for genomes from microbes that are present in low abundance in the sponge leading to a simplified reconstruction of secondary metabolite gene clusters present in these bacteria [184]. This strategy has been applied by Wilson et al. [185] for resolving the gene clusters encoding the machinery needed for the production of the polytheonamides produced by the candidate genus Entotheonella from the sponge Theonella swinhoei.

Inspired by these examples, homology-based screening could be further exploited to identify biosynthesis gene sequences that could lead to the identification of novel antimicrobial substances from Nature’s excessive diversity. Moreover, application of homology-based screening can benefit from publicly available metagenomic sequencing data and prediction tools for analyzing biosynthesis gene clusters, e.g., AntiSMASH (Antibiotics and Secondary Metabolite Analysis Shell) [186,187]. Application of sequence-based screening, however, is limited by the fact that the found sequences need to be related to known compounds, inherently limiting the potential for novelty. Furthermore, information on gene sequences is no guarantee that the acquisition of a complete gene pathway has been obtained [188]. Therefore, sequence-based methagenomics should ideally be complemented by chemical analysis to confirm whether the predicted compound exists and is fully functional (Figure 6).

Figure 6.

Figure 6

General overview of the strategies used to discover antimicrobial compounds from sponge-associated microorganisms.

7. Conclusions and Outlook

Sponge-associated microbes already offer a rich source of potent antimicrobial compounds against viruses, bacteria, protozoa and fungi, and currently available compounds are predominantly active against HIV-1, H1N1, nosocomial Gram positive bacteria, Escherichia coli, Plasmodium spp, Leishmania donovani, Trypanosoma brucei, Candida albicans and dermatophytic fungi. Streptomyces, Pseudovibrio, Bacillus, Aspergillus and Penicillium are the microbial genera associated with sponges from which potent antimicrobial compounds are most frequently isolated. However, none of the antimicrobial compounds highlighted in this review have been succcesfully marketed as pharmaceuticals. To clearly translate bioactivity of these important compounds it is crucial to further unravel their mode of actions and measure their level of toxicity, since the majority of these studies has been focused on in vitro bioassays and elucidation of the chemical structures only.

The known versatility of antimicrobial activities found in sponge-associated microorganims could easily be expanded even without considering additional sponge sampling campaigns. Bioactivity screens of identified compounds or undefined sponge extracts is often restricted to a specific antimicrobial activity. The selection, for instance, relies on the specific research activities of the groups involved in isolating the microbes [117]. Consequently, it is probably safe to assume that other potent antimicrobial properties from many sponge isolates and their bioactive compounds remain undetected. Therefore, known antimicrobial compounds and producer strains are a valuable source for additional antimicrobial activities screenings using different target types (viruses, bacteria, fungi, protozoa and beyond). In addition, sponge-derived strain collections that comprise isolates that tested negative for antimicrobial activity at first may have done so, because the compound of interest is not produced under standard laboratory conditions. Exposure of these strains to potential microbial targets may lead to recovery of bioactivity that would otherwise go unnoticed.

Ideally, researchers who isolate microbes from sponges will deposit them to publicly available culture collections so that laboratories with complementary expertise and interests could benefit and screen the deposited isolates for different antimicrobial activities. This will make exchange of materials and knowledge that can be obtained much more efficient. Importantly, a fair agreement on intellectual property rights needs to be established for translating this into reality. Lastly, the revolutionary advance of next generation sequencing technologies combined with more diversified heterologous expression systems (Figure 6) are expected to open up the large unexplored reservoir of antimicrobials produced by yet uncultivated sponge-associated microbes.

Acknowledgments

Anak Agung Gede Indraningrat receives a PhD fellowship from the Indonesia Endowment Fund for Education (LPDP), grant number 20140812021557. This work was also supported by the EC grant “BluePharmTrain” (grant agreement no. 607786).

Author Contributions

Anak Agung Gede Indraningrat and Detmer Sipkema conceived the idea for the review, Anak Agung Gede Indraningrat compiled literatures, drew figures, and wrote the manuscript. Detmer Sipkema and Hauke Smidt checked and improved the manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

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