Abstract
Background and Purpose:
Fusarium species are commonly resistant to many antifungal drugs. The limited therapeutic options available have led to a surge of research efforts aimed at discovering novel antifungal compounds in recent decades. This study aimed to assess the in vitro antifungal activity of plant-based biosynthesized selenium nanoparticles (Se NPs) and six comparators against a set of clinical Fusarium strains.
Materials and Methods:
In vitro antifungal activity of Se NPs synthesized using plant extracts of Allium paradoxum, Crocus caspius, Pistacia vera L. hull, Vicia faba L. hull and Heracleum persicum, as well as six common antifungal drugs, namely voriconazole, itraconazole, amphotericin B, posaconazole, natamycin, and caspofungin were evaluated against 94 clinical Fusarium strains using broth microdilution according to Clinical and Laboratory Standards Institute guideline.
Results:
The obtained results were intriguing since all five types of biosynthesized Se NPs demonstrated significantly higher antifungal activity, compared to antifungal drugs. It was found that Se NPs synthesized by V. faba L. hull extract (0.03 μg/ml) had the lowest geometric mean minimum inhibitory concentration value followed by Se NPs synthesized by P. vera L. hull extract (0.25 μg/ml), A. paradoxum extract (0.39 μg/ml), C. caspius extract (0.55 μg/ml), and H. persicum extract (0.9 μg/ml).
Conclusion:
Plant-based Se NPs demonstrated supreme antifungal activity and could be considered promising antifungal agents for Fusarium infections. However, tests, such as toxicity and in vivo tests are needed before the product can be used in clinical settings.
Keywords: Antifungal activity, Fusarium species, Se NPs, Plant extract
Introduction
Fungal pathogens pose a serious threat to public health, affecting at least 1.5 million people worldwide each year [ 1 , 2 ]. Resistance to conventional antifungal drugs has emerged as a global public health concern, severely limiting available treatment options [ 3 - 6 ]. Furthermore, since fungal and human cells are so similar, it is difficult to discover and develop new and effective antifungal drugs [ 7 , 8 ].
Fusarium is a large and remarkably diverse genus of saprophytic fungi found throughout nature [ 9 ]. Fusarium species are important phytopathogenic and mycotoxin-producing fungi [ 10 , 11 ]. They are also opportunistic fungi that cause a wide range of infections, from superficial and localized infections, such as onychomycosis and keratitis in healthy people to fatal systemic infections in severely ill people [ 12 - 14 ].
In the United States and Europe, Fusarium is the second most common mold-causing human infection [ 15 - 17 ]. This fungal genus has high levels of intrinsic resistance to commonly available antifungal agents, posing a serious challenge to healthcare systems all over the world [ 15 , 17 ]. Since Fusarium species are frequently resistant to many antifungal drugs, and since there is a limited therapeutic repository for these fungal infections, research focused on finding novel and potent antifungal compounds as well as alternatives are urgently needed [ 12 , 18 - 20 ].
Development of nanotechnology-based therapies in recent years has opened up new avenues for the treatment of drug-resistant fungal infections. Due to their nanometer size and large surface areas, nanoparticles have unique physicochemical properties that increase interactions with microbial cells and significantly influence their antimicrobial effects [ 21 , 22 ].
Selenium is a trace element that is essential for human and animal health, and it is involved in antioxidant defense, metabolism, and detoxification. Due to their low toxicity, high biodegradability, and bioavailability as well as anticancer, antidiabetic, antioxidant, antibacterial, antiprotozoal, antiviral, antifungal, and antibiofilm properties, selenium nanoparticles (Se NPs) are among the most appealing nanomaterials in biomedicine [ 23 , 24 ].
According to some studies, the antimicrobial activity of Se NPs is often attributed to the generation of reactive oxygen species, which can damage the DNA and cell membrane. However, the precise antimicrobial mechanisms of Se NPs have not been fully elucidated, and more research is needed. According to previous research, Se NPs can be synthesized through chemical, physical, or biological processes [ 25 - 28 ]. However, green synthesis or biologically synthesized Se NPs using microorganisms or plant extracts as natural reducing agents provides novel, simple, low-cost, non-toxic, and environment-friendly methods for the production of Se NPs [ 29 - 32 ].
Some plants contain a high concentration of phytochemical compounds with important biological and medicinal properties. The efficiency and capability of these compounds as nanoparticle reductants in green synthesis have previously been demonstrated [ 31 - 33 ]. The current study aimed to assess the in vitro antifungal activity of Se NPs made from extracts of Allium paradoxum, Crocus caspius, Pistacia vera L. hull, Vicia faba L. hull, and Heracleum persicum, as well as six antifungal drugs, namely, voriconazole, itraconazole, amphotericin B, posaconazole, natamycin, and caspofungin against a collection of clinical Fusarium strains.
Materials and Methods
Strains
In this study, 94 clinical isolates of Fusarium were examined. Isolates were collected from different medical mycology centers in Iran between 2019 and 2022 [ 34 ]. The most isolates were recovered from nail samples (58.51%, 55/94), followed by cornea (40.43%, 38/94) and Sinus (1.06%, 1/94). Partial sequencing of the translation elongation factor 1-alpha (TEF-1α) identified all Fusarium isolates at the species level.
Synthesis of plant-based selenium nanoparticles
The plant-based Se NPs used in this study were synthesized by the Department of Medicinal Chemistry at the School of Pharmacy and Pharmaceutical Sciences Research Centre of Mazandaran University of Medical Sciences, Sari, Iran [ 31 , 32 ]. The plants A. paradoxum, C. caspius, P. vera L. hull, V. faba L. hull, and H. persicum were dried in daylight, cut into small pieces (2-3 mm), and stored at room temperature. Each plant (10 g) was combined with 80 mL of deionized water and heated at 50 °C for 1 h. The mixture was then sonicated for 30 min and filtered through the Whatman filter paper. In the process of Se NPs biosynthesis using plant extracts, 17.3 mg of Na2SeO3 was dissolved in 10 mL of deionized water and stirred at 45-50 °C and 500 rpm. Subsequently, 5 mL of the aqueous extract was added to the reaction mixture drop by drop. After two days, the color of the reaction changed from colorless to reddish, indicating the reduction of Se ions.
Antifungal susceptibility testing
The in vitro antifungal activities of biosynthesized Se NPs using plant extracts of A. paradoxum (A-Se NPs), C. caspius (C-Se NPs), P. vera L. hull (P-Se NPs), V. faba L. hull (V-Se NPs), and H. persicum (H-Se NPs) as well as six routine antifungal drugs, including itraconazole (Janssen, Beerse, Belgium), posaconazole (Pfizer, Sandwich, United Kingdom), voriconazole (Pfizer, Sandwich, United Kingdom), natamycin (Sigma-Aldrich, Steinheim, Germany), amphotericin B (Bristol-Myers-Squib, Woerden, The Netherlands), and caspofungin (Merck Sharp & Dohme BV) were determined against 94 clinical Fusarium isolates. It was performed by using broth microdilution according to the Clinical and Laboratory Standards Institute M38-A3 [ 35 ].
The final concentrations of agents in the wells ranged from 0.016 to 16 μg/ml for V-Se NPs, A-Se NPs, P-Se NPs, C-Se NPs, H-Se NPs, amphotericin B, voriconazole, natamycin, posaconazole, itraconazole, and 0.008 to 8 μg/ml for caspofungin.
The Fusarium isolates were cultured on Sabouraud dextrose agar (Difco Laboratories, Detroit, MI, USA) and incubated at 35 °C for 5 to 7 days for adequate sporulation. Suspensions were diluted at 1:50 in RPMI 1640 medium to obtain final inoculum between 0.4 × 104 to 5 × 104 CFU/ml. Plates were incubated at 35 °C, and minimum inhibitory concentrations (MICs) and minimum effective concentrations (MECs) were read after 48 h.
The MIC was determined visually as the lowest concentration of agent that resulted in 100% inhibition of fungal growth while for caspofungin MEC was microscopically determined as the lowest concentration of drug that resulted in the growth of compact hyphal forms compared with growth control. Candida krusei (ATCC 6258), Candida parapsilosis (ATCC 22019), and Aspergillus flavus (ATCC 2004304) served as quality control strains.
Results
All Fusarium strains were previously identified using TEF1 partial gene analysis [ 34 ].
The species used in the study belonged to the Fusarium solani species complex (n=52), F. fujikuroi species complex (n=33), F. oxysporum species complex (n=7), F. incarnatum equiseti species complex (n=1), and F. sambucinum species complex (n=1) (Table 1). The geometric mean (GM) MICs/MECs, MIC/MEC ranges, MIC50/MEC50, and MIC90/MEC90 distributions of the tested compounds are shown in Table 2 and Table 3.
Table 1.
Sources and the number of the Fusarium isolates based on the species complexes
| Fusarium complexes | Species | Source | No. |
|---|---|---|---|
| F. fujikuroi species complex (n=33) | F. proliferatum | Nail | 15 |
| Cornea | 6 | ||
| Sinus | 1 | ||
| F. fujikuroi | Nail | 3 | |
| F. acutatum | Nail | 1 | |
| F. verticillioides | Nail | 5 | |
| F. thapsinum | Cornea | 2 | |
| F. solani species complex (n=52) | F. falciforme | Nail | 2 |
| Cornea | 3 | ||
| F. keratoplasticum | Nail | 6 | |
| F. solani sensu stricto | Cornea | 22 | |
| Nail | 19 | ||
| F. sambucinum species complex (n=1) | F. brachygibbosum | Cornea | 1 |
| F. incarnatum equiseti species complex (n=1) | F. equiseti | Nail | 1 |
| F. oxysporum species complex (n=7) | F. oxysporum | Cornea | 4 |
| Nail | 3 |
Table 2.
In vitro susceptibilities of plant-based selenium nanoparticles in comparison with six antifungal drugs against 94 clinical Fusarium isolates
| Fusarium species | Evaluated compounds | MIC50 (μg/ml) | MIC90 (μg/ml) | MIC range (μg/ml) | GM (μg/ml) | Mode (μg/ml) |
|---|---|---|---|---|---|---|
| Total Fusarium isolates (n=94) | A-Se NPs | 0.5 | 2 | 0.016-8 | 0.39 | 1 |
| C-Se NPs | 0.5 | 4 | 0.016-8 | 0.55 | 0.5 | |
| P-Se NPs | 0.25 | 4 | 0.016-16 | 0.25 | 0.5 | |
| V-Se NPs | 0.032 | 0.125 | 0.016-0.25 | 0.03 | 0.016 | |
| H-Se NPs | 1 | 4 | 0.016-8 | 0.9 | 1 | |
| VRC | 4 | 8 | 0.25-16 | 3.25 | 4 | |
| ITC | 16 | 16 | 0.032-16 | 13.01 | 16 | |
| AMB | 1 | 4 | 0.125-16 | 1.05 | 1 | |
| NAT | 4 | 8 | 0.125-16 | 3.91 | 8 | |
| CAS | 8 | 8 | 0.064-8 | 7 | 8 | |
| POS | 8 | 16 | 0.25-16 | 5.29 | 8 | |
| F. solani complex (n=52) | A-Se NPs | 1 | 4 | 0.016-8 | 0.56 | 1 |
| C-Se NPs | 1 | 4 | 0.016-8 | 0.64 | 2 | |
| P-Se NPs | 0.5 | 8 | 0.016-16 | 0.46 | 0.5 | |
| V-Se NPs | 0.032 | 0.125 | 0.016-0.25 | 0.03 | 0.016 | |
| H-Se NPs | 1 | 8 | 0.064-8 | 1.32 | 1 | |
| VRC | 4 | 8 | 0.25-16 | 3.74 | 8 | |
| ITC | 16 | 16 | 0.032-16 | 11.93 | 16 | |
| AMB | 0.5 | 2 | 0.125-16 | 0.67 | 0.5 | |
| NAT | 8 | 8 | 0.5-16 | 5.15 | 8 | |
| CAS | 8 | 8 | 0.064-8 | 6.46 | 8 | |
| POS | 8 | 16 | 0.5-16 | 6.55 | 16 | |
| F. fujikuroi complex (n=33) | A-Se NPs | 0.25 | 1 | 0.016-4 | 0.23 | 0.5 |
| C-Se NPs | 0.5 | 2 | 0.016-4 | 0.48 | 0.5 | |
| P-Se NPs | 0.064 | 1 | 0.016-4 | 0.1 | 0.016 | |
| V-Se NPs | 0.032 | 0.125 | 2-16 | 0.03 | 0.016 | |
| H-Se NPs | 0.5 | 4 | 0.064-8 | 0.56 | 0.25 | |
| VRC | 4 | 8 | 1-8 | 2.74 | 4 | |
| ITC | 16 | 16 | 8-16 | 14.1 | 16 | |
| AMB | 2 | 8 | 0.125-16 | 1.72 | 1 | |
| NAT | 4 | 8 | 0.125-8 | 2.41 | 4 | |
| CAS | 8 | 8 | 4-8 | 7.67 | 8 | |
| POS | 4 | 16 | 0.25-16 | 4.17 | 16 | |
| F. oxysporum complex (n=7) | A- Se NPs | - | - | 0.125-2 | 0.37 | 0.125 |
| C- Se NPs | - | - | 0.5-1 | 0.61 | 0.5 | |
| P- Se NPs | - | - | 0.125-0.5 | 0.18 | 0.125 | |
| V- Se NPs | - | - | 0.016-0.064 | 0.03 | 0.064 | |
| H- Se NPs | - | - | 0.5-2 | 0.6 | 0.5 | |
| VRC | - | - | 1-8 | 2.43 | 2 | |
| ITC | - | - | 16 | 16 | 16 | |
| AMB | - | - | 0.5-16 | 2.69 | 2 | |
| NAT | - | - | 2-8 | 4 | 8 | |
| CAS | - | - | 8 | 8 | 8 | |
| POS | - | - | 0.5-16 | 4.41 | 8 | |
| F. incarnatum equiseti species complex (n=1) | A-Se NPs | - | - | 0.25 | - | - |
| C-Se NPs | - | - | 0.5 | - | - | |
| P-Se NPs | - | - | 1 | - | - | |
| V-Se NPs | - | - | 0.016 | - | - | |
| H-Se NPs | - | - | 2 | - | - | |
| VRC | - | - | 4 | - | - | |
| ITC | - | - | 16 | - | - | |
| AMB | - | - | 1 | - | - | |
| NAT | - | - | 8 | - | - | |
| CAS | - | - | 8 | - | - | |
| POS | - | - | 8 | - | - | |
| F. sambucinum species complex (n=1) | A-Se NPs | - | - | 0.125 | - | - |
| C-Se NPs | - | - | 0.016 | - | - | |
| P-Se NPs | - | - | 0.125 | - | - | |
| V-Se NPs | - | - | 0.016 | - | - | |
| H-Se NPs | - | - | 0.016 | - | - | |
| VRC | - | - | 4 | - | - | |
| ITC | - | - | 16 | - | - | |
| AMB | - | - | 1 | - | - | |
| NAT | - | - | 8 | - | - | |
| CAS | - | - | 8 | - | - | |
| POS | - | - | 2 | - | - |
MIC: minimum inhibitory concentration, GM: geometric mean, A-Se NPs: A. paradoxum-selenium nanoparticles, C-Se NPs: C. caspius-selenium nanoparticles, P-Se NPs: P. vera L. hull-selenium nanoparticles, V-Se NPs: V. faba L. hull-selenium nanoparticles, H-Se NPs: H. persicum-selenium nanoparticles, VRC: voriconazole, ITC: itraconazole, AMB: amphotericin B, NAT: natamycin, CAS: caspofungin, POS: posaconazole
Table 3.
Minimum inhibitory concentrations of five Se NPs and six antifungal drugs on 94 clinical Fusarium isolates
| Fusarium species | Evaluated compounds | MIC distribution (μg/ml) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0.016 | 0.032 | 0.064 | 0.125 | 0.25 | 0.5 | 1 | 2 | 4 | 8 | 16 | ||
| Total Fusarium isolates (n=94) | A-Se NPs | 6 | 2 | 3 | 16 | 15 | 17 | 21 | 6 | 4 | 4 | |
| C-Se NPs | 6 | 3 | 2 | 10 | 10 | 20 | 12 | 16 | 12 | 3 | ||
| P-Se NPs | 15 | 5 | 7 | 18 | 7 | 18 | 6 | 2 | 9 | 5 | 2 | |
| V-Se NPs | 43 | 19 | 20 | 11 | 1 | |||||||
| H-Se NPs | 1 | 2 | 6 | 12 | 18 | 21 | 15 | 12 | 7 | |||
| VRC | 2 | 3 | 13 | 14 | 34 | 27 | 1 | |||||
| ITC | 1 | 1 | 1 | 11 | 80 | |||||||
| AMB | 6 | 5 | 23 | 30 | 14 | 9 | 2 | 5 | ||||
| NAT | 1 | 1 | 5 | 8 | 11 | 22 | 44 | 2 | ||||
| CAS | 1 | 1 | 9 | 83 | ||||||||
| POS | 2 | 6 | 2 | 14 | 15 | 28 | 27 | |||||
| F. solani complex (n=52) | A-Se NPs | 3 | 1 | 1 | 5 | 9 | 6 | 15 | 5 | 3 | 4 | |
| C-Se NPs | 4 | 2 | 1 | 6 | 5 | 5 | 6 | 11 | 9 | 3 | ||
| P-Se NPs | 6 | 3 | 1 | 8 | 2 | 13 | 4 | 1 | 7 | 5 | 2 | |
| V-Se NPs | 22 | 11 | 11 | 7 | 1 | |||||||
| H-Se NPs | 1 | 1 | 4 | 10 | 11 | 10 | 9 | 6 | ||||
| VRC | 2 | 3 | 2 | 7 | 16 | 21 | 1 | |||||
| ITC | 1 | 1 | 1 | 5 | 44 | |||||||
| AMB | 5 | 4 | 19 | 17 | 4 | 1 | 1 | 1 | ||||
| NAT | 4 | 1 | 2 | 12 | 31 | 2 | ||||||
| CAS | 1 | 1 | 7 | 43 | ||||||||
| POS | 2 | 8 | 8 | 17 | 17 | |||||||
| F. fujikuroi complex (n=33) | A-Se NPs | 3 | 1 | 2 | 7 | 5 | 9 | 5 | 1 | |||
| C-Se NPs | 1 | 1 | 1 | 4 | 5 | 9 | 4 | 5 | 3 | |||
| P-Se NPs | 9 | 2 | 6 | 4 | 5 | 3 | 1 | 1 | 2 | |||
| V-Se NPs | 16 | 7 | 6 | 4 | ||||||||
| H-Se NPs | 1 | 5 | 8 | 4 | 8 | 3 | 3 | 1 | ||||
| VRC | 10 | 3 | 15 | 5 | ||||||||
| ITC | 6 | 27 | ||||||||||
| AMB | 1 | 1 | 3 | 11 | 7 | 6 | 1 | 3 | ||||
| NAT | 1 | 1 | 1 | 7 | 6 | 9 | 8 | |||||
| CAS | 2 | 31 | ||||||||||
| POS | 2 | 2 | 2 | 4 | 7 | 8 | 8 | |||||
| F. oxysporum complex (n=7) | A-Se NPs | 3 | 2 | 1 | 1 | |||||||
| C-Se NPs | 5 | 2 | ||||||||||
| P-Se NPs | 5 | 2 | ||||||||||
| V-Se NPs | 3 | 1 | 3 | |||||||||
| H-Se NPs | 4 | 2 | 1 | |||||||||
| VRC | 1 | 4 | 1 | 1 | ||||||||
| ITC | 7 | |||||||||||
| AMB | 1 | 3 | 2 | 1 | ||||||||
| NAT | 3 | 1 | 3 | |||||||||
| CAS | 7 | |||||||||||
| POS | 2 | 3 | 2 | |||||||||
| F. incarnatum equiseti species complex (n=1) | A-Se NPs | 1 | ||||||||||
| C-Se NPs | 1 | |||||||||||
| P-Se NPs | 1 | |||||||||||
| V-Se NPs | 1 | |||||||||||
| H-Se NPs | 1 | |||||||||||
| VRC | 1 | |||||||||||
| ITC | 1 | |||||||||||
| AMB | 1 | |||||||||||
| NAT | 1 | |||||||||||
| CAS | 1 | |||||||||||
| POS | 1 | |||||||||||
| F. sambucinum species complex (n=1) | A-Se NPs | 1 | ||||||||||
| C-Se NPs | 1 | |||||||||||
| P-Se NPs | 1 | |||||||||||
| V-Se NPs | 1 | |||||||||||
| H-Se NPs | 1 | |||||||||||
| VRC | 1 | |||||||||||
| ITC | 1 | |||||||||||
| AMB | 1 | |||||||||||
| NAT | 1 | |||||||||||
| CAS | 1 | |||||||||||
| POS | 1 | |||||||||||
MIC: minimum inhibitory concentration, MEC: minimum effective concentration, A-Se NPs: A. paradoxum-selenium nanoparticles, C-Se NPs: C. caspius-selenium nanoparticles, P-Se NPs: P. vera L. hull-selenium nanoparticles, V-Se NPs: V. faba L. hull-selenium nanoparticles, H-Se NPs: H. persicum-selenium nanoparticles, VRC: voriconazole, ITC: itraconazole, AMB: amphotericin B, NAT: natamycin, CAS: caspofungin, POS: posaconazole
The obtained results were extremely intriguing since all five types of biosynthesized Se NPs demonstrated significantly higher antifungal activity, compared to routine antifungal drugs in the clinical settings.
According to GM MICs/MECs values, V-Se NPs (0.03 μg/ml) showed the lowest GM MICs/MECs values, followed by P-Se NPs (0.25 μg/ml), A-Se NPs (0.39 μg/ml), C-Se NPs (0.55 μg/ml), H-Se NPs (0.9 μg/ml), amphotericin B (1.05 μg/ml), voriconazole (3.25 μg/ml), natamycin (3.91 μg/ml), posaconazole (5.29 μg/ml), caspofungin (7 μg/ml), and itraconazole (13.01 μg/ml). Moreover, the comparison of the susceptibility results revealed that the Fusarium strains had the lowest MIC90/MEC90 values for V- Se NPs (0.125 μg/ml), followed by A-Se NPs (2 μg/ml), P-Se NPs (4 μg/ml), C-Se NPs (4 μg/ml), H-Se NPs (4 μg/ml), amphotericin B (4μg/ml), voriconazole (8 μg/ml), natamycin (8 μg/ml), caspofungin (8 μg/ml), posaconazole (16 μg/ml), and itraconazole (16 μg/ml).
Discussion
Fusarium is a globally distributed multidrug-resistant genus that has the potential to cause a wide range of infections in humans [ 19 ]. In the present study, the inhibitory activity of five plant-based biosynthesized Se NPs and six common antifungal drugs were tested against 98 clinical Fusarium strains. Remarkably, it was discovered that the antifungal activity of plant-based Se NPs was superior to that of voriconazole, itraconazole, amphotericin B, posaconazole, natamycin, and caspofungin in vitro.
The lowest GM MICs and the highest antifungal activity among the biosynthesized selenium nanoparticles belonged to V-S eNPs (0.03 μg/ml), followed by P-Se NPs (0.25 μg/ml), A-Se NPs (0.39 μg/ml), C-Se NPs (0.55 μg/ml), and H-Se NPs (0.9 μg/ml). Additionally, the MIC50 values of all five types of biosynthesized Se NPs against Fusarium isolates were significantly lower than those of the drugs of choice for the treatment of invasive fusariosis, which were amphotericin B (MIC50, 1 μg/ml) and voriconazole (MIC50, 4 μg/ml).
Selenium has antimicrobial properties and has been shown to inhibit the growth of fungi and bacteria. Selenium derivatives, such as selenium sulphide, are commonly used in the treatment of pityriasis versicolor [ 36 - 40 ]. Nanotechnology advancements in recent years have provided a safe strategy for the reduction of selenium toxicity. When compared to inorganic and organic forms, Se NPs have lower toxicity and higher bioavailability [ 24 , 41 - 43 ].
Several studies have shown that biogenic selenium nanoparticles have antifungal activity [ 29 , 44 , 45 ]. Shakibaie et al. investigated the antifungal activity of Bacillus species synthesized selenium nanoparticles against A. fumigatus and Candida albicans, and the measured MICs for C. albicans (70 μg/ml) and A. fumigatus (100 μg/ml) showed that the biogenic Se NPs had good antifungal activity [ 44 ]. Shahverdi et al. also investigated the antifungal activity of Klebsiella pneumoniae-produced selenium nanoparticles against clinical isolates of the Malassezia and Aspergillus genus. The MICs for all fungal strains were within the range of 10-260 g/ml, with M. sympodialis, M. furfur, and A. terreus showing the highest antifungal activity [ 45 ].
Another study assessed the antifungal activity of Se NPs synthesized by Lactobacillus acidophilus in controlling wheat crown and root rot diseases caused by Fusarium species, and biogenic Se NPs successfully inhibited fungal growth at concentrations ranging from 20 to 40 μg/ml [ 46 ]. Furthermore, several studies on the synthesis of nanoparticles using plant extracts have been published [ 47 - 49 ].
There have been few studies on the antifungal activity of biosynthesized Se NPs derived from plant extracts. Gunti et al. demonstrated that biosynthesized Se NPs derived from Emblica officinalis fruit extract had strong antifungal activity. The MIC values were found to be between 07.50 ± 1.32 and 25.50 ± 2.78 μg/ml. The lowest and highest found MIC values were 07.50 ± 1.32 μg/ml against Rhizopus stolonifer and 25.50 ± 2.78 μg/ml against A. oryzae, respectively [ 50 ].
In another study, Kokila et al. biosynthesized Se NPs from Diospyros montana extract and reported antimicrobial activity in the form of zone of inhibition values of 08, 07, and 08 mm against Staphylococcus aureus, Escherichia coli, and A. niger, respectively [ 51 ]. Ali et al. also investigated the antifungal activity of Se NPs extracted from Capparis decidua fruit against C. albicans and discovered that biosynthesized Se NPs have a high antifungal activity [ 52 ].
In the present study, all five biosynthesized Se NPs derived from plant extracts outperformed the commonly used antifungal drugs. Biosynthesized Se NPs, particularly nanoparticles made from V. faba L. hull, P. vera L. hull, and A. paradoxum plant extracts demonstrated potent antifungal activity against clinical Fusarium isolates in vitro. In addition to the antifungal properties of metal ions and the size of the nanoparticles, the antifungal activity of Se NPs in vitro may be attributed to the phytochemical composition of the plant extracts used for green synthesis, as these factors may affect their bioavailability and antimicrobial activity [ 30 , 32 ].
Conclusion
Plant-based Se NPs demonstrated supreme antifungal activity and could be considered promising antifungal agents for Fusarium infections. However, tests, such as toxicity and in vivo tests, are needed before the product can be used in clinical settings.
Acknowledgments
This study was performed with the financial support of Mazandaran University of Medical Sciences, Sari, Iran grant number: 10319].
Author’s contribution
M. A., I. H., M. A. E, A. M. S. A. H. conceived, designed, and supervised the study. M. N., M. A., S. R. A., R. E. B., L. F. performed the experiments and wrote the draft. M. A., A. M. S. A. H., M. A. E., and I. H. designed the study, analyzed the data, and edited the manuscript draft. All authors read and approved the final version of the manuscript.
Conflicts of interest
The authors report no conflicts of interest.
Financial disclosure
None.
Ethical Approval
The current study was approved by the Ethics Committee of the Mazandaran University of Medical Sciences (IR.MAZUMS.REC.1400.423).
References
- 1.Loh JT, Lam KP. Fungal infections: Immune defense, immunotherapies and vaccines. Adv Drug Deliv Rev. 2023; 196:114775. doi: 10.1016/j.addr.2023.114775. [DOI] [PubMed] [Google Scholar]
- 2.Palmieri F, Koutsokera A, Bernasconi E, Junier P, von Garnier C, Ubags N. Recent Advances in Fungal Infections: From Lung Ecology to Therapeutic Strategies with a Focus on Aspergillus spp. Front Med. 2022; 9:832510. doi: 10.3389/fmed.2022.832510. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Vitiello A, Ferrara F, Boccellino M, Ponzo A, Cimmino C, Comberiati E, Zovi A, Clemente S, Sabbatucci M. Antifungal Drug Resistance: An Emergent Health Threat. Biomedicines. 2023;11(4):1063. doi: 10.3390/biomedicines11041063. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Fisher MC, Alastruey-Izquierdo A, Berman J, Bicanic T, Bignell EM, Bowyer P, Bromley M, Brüggemann R, Garber G, Cornely OA, Gurr SJ. Tackling the emerging threat of antifungal resistance to human health. Nat Rev Microbiol. 2022;20(9):557–71. doi: 10.1038/s41579-022-00720-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Abastabar M, Haghani I, Shokohi T, Hedayati MT, Aghili SR, Jedi A, Dadashi S, Shabanzadeh S, Hosseini T, Aslani N, Meis JF. Low in vitro antifungal activity of tavaborole against yeasts and molds from onychomycosis. Antimicrob Agents Chemother. 2018;62(12):10–128. doi: 10.1128/AAC.01632-18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Abastabar M, Jedi A, Guillot J, Ilkit M, Eidi S, Hedayati MT, Shokohi T, Daie Ghazvini R, Rezaei‐Matehkolaei A, Katiraee F, Javidnia J. In vitro activities of 15 antifungal drugs against a large collection of clinical isolates of Microsporum canis. Mycoses. 2019;62(11):1069–78. doi: 10.1111/myc.12986. [DOI] [PubMed] [Google Scholar]
- 7.Vanreppelen G, Wuyts J, Van Dijck P, Vandecruys P. Sources of antifungal drugs. J Fungi. 2023;9(2):171. doi: 10.3390/jof9020171. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Roy M, Karhana S, Shamsuzzaman M, Khan MA. Recent drug development and treatments for fungal infections. Braz J Microbiol. 2023;23:1–22. doi: 10.1007/s42770-023-00999-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Al-Hatmi AM, Meis JF, de Hoog GS. Fusarium: molecular diversity and intrinsic drug resistance. PLoS Pathog. 2016;12(4): e1005464. doi: 10.1371/journal.ppat.1005464. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Rampersad SN. Pathogenomics and management of Fusarium diseases in plants. Pathogens. 2020;9(5):340. doi: 10.3390/pathogens9050340. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Ekwomadu TI, Akinola SA, Mwanza M. Fusarium mycotoxins, their metabolites (free, emerging, and masked), food safety concerns, and health impacts. Int J Environ Res Public Health. 2021;18(22):11741. doi: 10.3390/ijerph182211741. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Al-Hatmi AM, de Hoog GS, Meis JF. Multiresistant Fusarium pathogens on plants and humans: solutions in (from) the antifungal pipeline? Infect Drug Resist. 2019;28:3727–37. doi: 10.2147/IDR.S180912. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Hof H. The medical relevance of Fusarium spp. J Fungi. 2020;6(3):117. doi: 10.3390/jof6030117. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Abastabar M, Al-Hatmi AM, Vafaei Moghaddam M, De Hoog GS, Haghani I, Aghili SR, Shokohi T, Hedayati MT, Daie Ghazvini R, Kachuei R, Rezaei-Matehkolaei A. Potent activities of luliconazole, lanoconazole, and eight comparators against molecularly characterized Fusarium species. Antimicrob Agents Chemother. 2018;62(5): e00009–18. doi: 10.1128/AAC.00009-18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Park BJ, Pappas PG, Wannemuehler KA, Alexander BD, Anaissie EJ, Andes DR, Baddley JW, Brown JM, Brumble LM, Freifeld AG, Hadley S. Invasive non-Aspergillus mold infections in transplant recipients, United States, 2001–2006. Emerg Infect Dis. 2011;17(10):1855. doi: 10.3201/eid1710.110087. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Kontoyiannis DP, Marr KA, Park BJ, Alexander BD, Anaissie EJ, Walsh TJ, Ito J, Andes DR, Baddley JW, Brown JM, Brumble LM. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis. 2010;50(8):1091–100. doi: 10.1086/651263. [DOI] [PubMed] [Google Scholar]
- 17.Salah H, Houbraken J, Boekhout T, Almaslamani M, Taj-Aldeen SJ. Molecular epidemiology of clinical filamentous fungi in Qatar beyond Aspergillus and Fusarium with notes on the rare species. Med Mycol. 2023;61(1):myac098. doi: 10.1093/mmy/myac098. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Tupaki‐Sreepurna A, Al‐Hatmi AM, Kindo AJ, Sundaram M, de Hoog GS. Multidrug‐resistant Fusarium in keratitis: a clinico‐mycological study of keratitis infections in Chennai, India. Mycoses. 2017;60(4):230–3. doi: 10.1111/myc.12578. [DOI] [PubMed] [Google Scholar]
- 19.Al-Hatmi AM, Bonifaz A, Ranque S, De Hoog GS, Verweij PE, Meis JF. Current antifungal treatment of fusariosis. Int J Antimicrob Agents. 2018;51(3):326–32. doi: 10.1016/j.ijantimicag.2017.06.017. [DOI] [PubMed] [Google Scholar]
- 20.Najafzadeh MJ, Dolatabadi S, de Hoog S, Esfahani MK, Haghani I, Aghili SR, Ghazvini RD, Rezaei-Matehkolaei A, Abastabar M, Al-Hatmi AM. Phylogenetic analysis of clinically relevant Fusarium species in Iran. Mycopathologia. 2020; 185:515–25. doi: 10.1007/s11046-020-00460-x. [DOI] [PubMed] [Google Scholar]
- 21.León-Buitimea A, Garza-Cervantes JA, Gallegos-Alvarado DY, Osorio-Concepción M, Morones-Ramírez JR. Nanomaterial-based antifungal therapies to combat fungal diseases aspergillosis, Coccidioidomycosis, Mucormycosis, and candidiasis. Pathogens. 2021;10(10):1303. doi: 10.3390/pathogens10101303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Joudeh N, Linke D. Nanoparticle classification, physicochemical properties, characterization, and applications: a comprehensive review for biologists. J Nanobiotechnology. 2022 ;20(1):262. doi: 10.1186/s12951-022-01477-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Genchi G, Lauria G, Catalano A, Sinicropi MS, Carocci A. Biological activity of selenium and its impact on human health. Int J Mol Sci. 2023;24(3):2633. doi: 10.3390/ijms24032633. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Hosnedlova B, Kepinska M, Skalickova S, Fernandez C, Ruttkay-Nedecky B, Peng Q, Baron M, Melcova M, Opatrilova R, Zidkova J, Sochor J. Nano-selenium and its nanomedicine applications: a critical review. Int J Nanomed. 2018;13 doi: 10.2147/IJN.S157541. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Filipović N, Ušjak D, Milenković MT, Zheng K, Liverani L, Boccaccini AR, Stevanović MM. Comparative study of the antimicrobial activity of selenium nanoparticles with different surface chemistry and structure. Front Bioeng Biotechnol. 2021; 8:624621. doi: 10.3389/fbioe.2020.624621. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Martínez-Esquivias F, Guzmán-Flores JM, Pérez-Larios A, González Silva N, Becerra-Ruiz JS. A review of the antimicrobial activity of selenium nanoparticles. J Nanosci Nanotechnol. 2021;21(11):5383–98. doi: 10.1166/jnn.2021.19471. [DOI] [PubMed] [Google Scholar]
- 27.Zhang H, Li Z, Dai C, Wang P, Fan S, Yu B, Qu Y. Antibacterial properties and mechanism of selenium nanoparticles synthesized by Providencia sp. DCX. Environ Res. 2021;194:110630. doi: 10.1016/j.envres.2020.110630. [DOI] [PubMed] [Google Scholar]
- 28.Bisht N, Phalswal P, Khanna PK. Selenium nanoparticles: A review on synthesis and biomedical applications. Mater Adv. 2022;3(3):1415–31. [Google Scholar]
- 29.Pescuma M, Aparicio F, Zysler RD, Lima E, Zapata C, Marfetán JA, Vélez ML, Ordoñez OF. Biogenic selenium nanoparticles with antifungal activity against the wood-rotting fungus Oligoporus pelliculosus. Biotechnology Reports. 2023;37: e00787. doi: 10.1016/j.btre.2023.e00787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Lazcano-Ramírez HG, Garza-García JJ, Hernández-Díaz JA, León-Morales JM, Macías-Sandoval AS, García-Morales S. Antifungal Activity of Selenium Nanoparticles Obtained by Plant-Mediated Synthesis. Antibiotics. 2023;12(1):115. doi: 10.3390/antibiotics12010115. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Alizadeh SR, Abbastabar M, Nosratabadi M, Ebrahimzadeh MA. High antimicrobial, cytotoxicity, and catalytic activities of biosynthesized selenium nanoparticles using Crocus caspius extract. Arab. J. Chem. 2023;16(6):104705. [Google Scholar]
- 32.Alizadeh S.R., Seyedabadi M., Montazeri M., Khan B.A., Ebrahimzadeh M.A. Allium paradoxum extract mediated green synthesis of SeNPs: Assessment of their anticancer, antioxidant, iron chelating activities, and antimicrobial activities against fungi, ATCC bacterial strains, Leishmania parasite, and catalytic reduction of methylene blue. Mater Chem Phys. 2023;296:127240. [Google Scholar]
- 33.Salih AM, Al-Qurainy F, Khan S, Nadeem M, Tarroum M, Shaikhaldein HO. Biogenic silver nanoparticles improve bioactive compounds in medicinal plant Juniperus procera in vitro. Front Plant Sci. 2022;13 doi: 10.3389/fpls.2022.962112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Nosratabadi M, Faeli L, Haghani I, Mohammadi R, Khodavaisy S, Kachuei R, Katiraee F, Aghili SR, Shokohi T, Hedayati MT, Nazeri M. In vitro antifungal susceptibility profile of Iranian Fusarium isolates: Emphasising on the potent inhibitory effect of efinaconazole compared to other drugs. Mycoses. 2023;66(3):258–75. doi: 10.1111/myc.13550. [DOI] [PubMed] [Google Scholar]
- 35.CLSI,edition. CLSI standard M38. 3rd ed. Clinical and Laboratory Standards Institute; 2019. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi. [Google Scholar]
- 36.Robinson HM, Yaffe SN. Selenium sulfide in treatment of pityriasis versicolor. J Am Med. Assoc. 1956;162(2):113–4. doi: 10.1001/jama.1956.72970190006007c. [DOI] [PubMed] [Google Scholar]
- 37.Cohen PR, Anderson CA. Topical selenium sulfide for the treatment of Hyperkeratosis. Dermatology and therapy. 2018; 8:639–46. doi: 10.1007/s13555-018-0259-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Tiekink ER. Therapeutic potential of selenium and tellurium compounds: opportunities yet unrealised. Dalton Transactions. 2012;41(21):6390–5. doi: 10.1039/c2dt12225a. [DOI] [PubMed] [Google Scholar]
- 39.Savin R. Diagnosis and treatment of tinea versicolor. Journal of family practice. 1996; 43(2):127–39. [PubMed] [Google Scholar]
- 40.Faergemann J. Management of seborrheic dermatitis and pityriasis versicolor. Am J Clin Dermatol. 2000;1: 75–80. doi: 10.2165/00128071-200001020-00001. [DOI] [PubMed] [Google Scholar]
- 41.Lin W, Zhang J, Xu JF, Pi J. The advancing of selenium nanoparticles against infectious diseases. Front Pharmacol. 2021;12:682284. doi: 10.3389/fphar.2021.682284. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42.Zhang T, Qi M, Wu Q, Xiang P, Tang D, Li Q. Recent research progress on the synthesis and biological effects of selenium nanoparticles. Front Nutr. 2023;10:1183487. doi: 10.3389/fnut.2023.1183487. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43.Au A, Mojadadi A, Shao JY, Ahmad G, Witting PK. Physiological Benefits of Novel Selenium Delivery via Nanoparticles. Int J Mol Sci. 2023;24(7):6068. doi: 10.3390/ijms24076068. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44.Shakibaie M, Mohazab NS, Mousavi SA. Antifungal activity of selenium nanoparticles synthesized by Bacillus species Msh-1 against Aspergillus fumigatus and Candida albicans. Jundishapur J Microbiol. 2015;8(9) doi: 10.5812/jjm.26381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Shahverdi AR, Fakhimi A, Mosavat G, Jafari-Fesharaki P, Rezaie S, Rezayat SM. Antifungal activity of biogenic selenium nanoparticles. World Appl Sci J. 2010;10(8):918–22. [Google Scholar]
- 46.El-Saadony MT, Saad AM, Najjar AA, Alzahrani SO, Alkhatib FM, Shafi ME, Selem E, Desoky ES, Fouda SE, El-Tahan AM, Hassan MA. The use of biological selenium nanoparticles to suppress Triticum aestivum L. crown and root rot diseases induced by Fusarium species and improve yield under drought and heat stress. Saudi J Biol Sci. 2021;28(8):4461–71. doi: 10.1016/j.sjbs.2021.04.043. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47.Hano C, Abbasi BH. Plant-based green synthesis of nanoparticles: Production, characterization and applications. Biomolecules. 2021;12(1):31. doi: 10.3390/biom12010031. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Adeyemi JO, Oriola AO, Onwudiwe DC, Oyedeji AO. Plant extracts mediated metal-based nanoparticles: Synthesis and biological applications. Biomolecules. 2022;12(5):627. doi: 10.3390/biom12050627. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49.Amini SM, Getso MI, Farahyar S, Khodavaisy S, Roudbary M, Mahabadi VP, Mahmoudi S. Antifungal activity of green-synthesized curcumin-coated silver nanoparticles alone and in combination with fluconazole and itraconazole against Candida and Aspergillus species. Curr Med Mycol. 2023;9(3):38. doi: 10.22034/cmm.2023.345125.1456. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 50.Gunti L, Dass RS, Kalagatur NK. Phytofabrication of selenium nanoparticles from Emblica officinalis fruit extract and exploring its biopotential applications: antioxidant, antimicrobial, and biocompatibility. Front microbiol. 2019; 10:931. doi: 10.3389/fmicb.2019.00931. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51.Kokila K, Elavarasan N, Sujatha V. Diospyros montana leaf extract-mediated synthesis of selenium nanoparticles and their biological applications. New J Chem. 2017;41(15):7481–90. [Google Scholar]
- 52.Ali SJ, Preetha S, Jeevitha M, Prathap L, Rajeshkumar S. Antifungal Activity of Selenium Nanoparticles Extracted from Capparis decidua Fruit against Candida albicans. J Evol Med Dent Sci. 2020;9(34):2452–6. [Google Scholar]