Novel pathways in bacteriocin synthesis by lactic acid bacteria with special reference to ethnic fermented foods

Abstract

Ethnic fermented foods are known for their unique aroma, flavour, taste, texture and other sensory properties preferred by every ethnic community in this world culturally as parts of their eatables. Some beneficial microorganisms associated with fermented foods have several functional properties and health-promoting benefits. Bacteriocins are the secondary metabolites produced by the microorganisms mostly lactic acid bacteria present in the fermented foods which can act as lantibiotics against the pathogen bacteria. Several studies have been conducted regarding the isolation and characterization of potent strains as well as their association with different types of bacteriocins. Collective information regarding the gene organizations responsible for the potent effect of bacteriocins as lantibiotics, mode of action on pathogen bacterial cells is not yet available. This review focuses on the gene organizations, pathways include for bacteriocin and their mode of action for various classes of bacteriocins produced by lactic acid bacteria in some ethnic fermented foods.

Introduction

Fermented foods are mostly ethnic-origin, which are known for their unique aroma, flavour, taste, texture and other sensory properties preferred by every ethnic community in this world culturally as parts of their eatables (Tamang, 2016a, 2020; Voidarou et al., 2021). Some microbial communities associated with fermented foods have functional properties such as production of antimicrobial compounds (Hernández-González et al., 2021), antioxidants (Menezes et al., 2020), probiotics (Marco et al., 2021), immunomodulators (Shahbazi et al., 2021), health-promoting benefits (Garcia-Gonzalez et al., 2021; Melini et al., 2019; Tamang et al., 2016b) and therapeutic uses to combat diseases (Dimidi et al., 2019; Rezac et al., 2018). Many ethnic fermented foods are prepared traditionally by spontaneous or natural fermentation from raw or boiled substrates of plants, animal flesh and milk (Tamang et al., 2020), which facilitate the growth of diverse types of culturable and unculturable microbiota including major domains of bacteria, yeasts, filamentous moulds, virus and archaea (Bhutia et al., 2021; Das and Tamang, 2021; Kharnaior and Tamang, 2021; Leech et al., 2020). Till date, the most commonly reported bacteria from fermented foods are lactic acid bacteria (LAB) for their various fermentative roles imparting functional and other health-promoting benefits mainly in acidic fermented foods including dairy products (Marco et al., 2021; Moh et al., 2021; Tamang et al., 2005, 2008, 2009). LAB belong to phylum Firmicutes are Gram-positive, acid-tolerant and non-spore-formers that bio-synthesize several metabolites and bioactive compounds (Teneva-Angelova et al., 2018). Generally four families of LAB viz. Lactobacillaceae, Streptococcaceae, Streptococcaceae, and Enterococcaceae are reported from fermented foods (Ashaolu and Reale, 2020; Holzapfel and Wood, 2014), which are represented by dominant genera such as Lacticaseibacillus, Lentilactobacillus, Levilactobacillus, Loigolactobacillus, Lactococcus, Leuconostoc, Pediococcus, Enterococcus, Streptococcus, Weissella, Tetragenococcus, Oenococcus, Alkalibacterium, Carnobacterium, Fructobacillus, and Vagococcus (Mathur et al., 2020; Pradhan and Tamang, 2019; Shangpliang and Tamang, 2021; Zheng et al., 2020). Most of the LAB present in the fermented foods are generally regarded as safe (GRAS) food-grade bacteria (Mathur et al., 2020; USFDA, 1988), and also listed in the microbial food cultures (MFC) safety inventory (Bourdichon et al., 2019; Tamang et al., 2021).

Secondary metabolites produced by bacteria are being exploited as useful bioactive molecules (Chaudhary et al., 2021; Pham et al., 2019), since some bacteria are very diverse both phylogenetically and functionally, carrying out complex metabolic transformations (Diether and Willing, 2019). This metabolic versatility can act as a boon for pharmaceutical and food industries. Recently, demand for minimally processed food products with zero chemicals (Dávila-Aviña et al., 2015) is increasing since as the chemical preservatives have some harmful effect to consumers (Chemat et al., 2017; Zhong et al., 2018). One such bio-preservation strategy is the use of bacteriocins or bacteriocins-producing starter cultures to preserve the intended foods (Ng et al., 2020; Silva et al., 2018; Soltani et al., 2021). Importance of bacteriocin produced by LAB have been reviewed earlier (Hernández-González et al. 2021; Kaškonienė et al., 2017; Mokoena, 2017), however, information regarding the gene organizations responsible for potent effect of bacteriocins as lantibiotics, mode of action on pathogen bacterial cells is not yet available. Hence, the present review is aimed to update on the gene organizations, novel pathways for bacteriocin synthesis and their mode of action by lactic acid bacteria isolated from some ethnic fermented foods.

Bacteriocin

Bacteriocin was first discovered by Gratia (1925) namely “colicine” as it showed activity against E. coli. Later in 1953, Jacob et al. (1953) coined the term bacteriocin, showing promises toward the development of microbial antibiotics. Several Gram-positive (Malanovic et al., 2016) and Gram-negative (Duperthuy, 2020) are known to produce substances during their growth, mainly protein or polypeptides that possess antimicrobial activities (Raheem and Straus, 2019), and make up a heterogeneous group of peptides with respect to size, structure, antimicrobial potency, mode of action, immunity mechanism and target cell receptors (Kumar et al., 2018; Lei et al., 2019). Bacteriocins are ribosomal-synthesized antimicrobial peptides produced by bacterial strains (Negash and Tsehai, 2020), which are lethal to closely related species of producer bacteria but being protected by self-immunity (Simons et al., 2020). Bacteriocin plays a major role as competitor, communication molecule among microbial community (Schulz-Bohm et al., 2017) and quorum sensing (Zhao et al., 2020). Some bacteria produce bacteriocin-like compounds but not yet characterized, such bacteriocins are referred as bacteriocin-like inhibitory substances (BLIS) (Choeisoongnern et al., 2020; El-Gendy et al., 2021). The most important bacteriocin class is lantibiotics with an unusual amino acid i.e., lanthionine (Lan) (Islam et al., 2012). More than 25 lantibiotics have been described out of which nisin is widely studied lantibiotic (Garcia-Gutierrez et al., 2020). Nisin is the most utilized antimicrobial peptide produced by Lactococcus lactis strains, due to its excellent features as a food preservative, including high activity against Gram-positive food pathogens (Kitagawa et al., 2019).

Biosynthesis of bacteriocin

Bacteriocins are synthesized in a very specific pathway, which includes the pre-bacteriocin production and subsequently cleavage of the pre-peptide at specific processing site that removes the leader sequence and translocation of the pro-bacteriocin outside the cell membrane (Simons et al., 2020). Specific gene encoding for the synthesis of bacteriocins are clustered in one or two operons, which consist of different components, located on plasmids (chromosome) or in transposons inserted in the chromosome (Drider et al., 2006; Wirawan et al., 2007). First components are the structural gene, which encodes the pre-probacteriocin, that contains an N-terminal (the leader sequence doubleglycine type or peptide signal type sequences type) (Samal, 2013). The two conserved glycines are present at its C-terminus, which is recognized by ABC transporters for processing the leader sequence and helps in the secretion of the mature bacteriocin to the extracellular medium. In all these processes, signal peptide type sequence (SP) plays a significant role in processing and secretion of bacteriocins through the general transport path (GSP). Second components are immunity gene, which is of small proteins consists of 51–154 amino acids. These genes help in protecting the producing strain of the bacteriocin itself. Third components are the genes that encodes protein which is responsible for processing, transport and secretion of the pre-probacteriocin. Fourth components are modification gene, which encodes the enzyme which is responsible for post-translational modifications of the probacteriocin. Fifth components are regulatory gene, which encodes the gene which involved in the regulation of bacteriocin synthesis (Perez et al., 2018; Skaugen et al., 2003). The complete process of bacteriocin production and secretion goes through the signal transduction systems, which consists of three components such as Inductor peptide (IP), response regulatory protein (RR), and sensor histidine protein kinase (HPK) (Fig. 1).

Fig. 1.

Biosynthesis of nisin through the signal transduction systems, which consists of three components such as inductor peptide (IP), response regulatory protein (RR), and sensor histidine protein kinase (HPK) (Fig. 1)

(adopted from Cheigh et al., 2005)

There are two models that explain the induction process, the inducing peptide and signal transduction mechanism (Straume et al., 2007). The IPs (small cationic molecules) that form an amphiphilic α helix and also work as signal of the regulatory systems (or “quorum sensing”) which help in controlling the biosynthesis of certain bacteriocins (Mokoena, 2017). The first model explains that the IP is produced consistently in small amounts, and accumulates progressively during the growth of the cell, and when required it increases the expression of the bacteriocin gene (Lafuente-Rincón et al., 2016). The second model explains the induction process, IP occurs at a level below the required level of self induction, and in certain environmental factors temporarily increases its production, so whenever the required level exceeds, it will induce its own synthesis by expressing the remaining gene from the bacteriocin gene cluster (Lafuente-Rincón et al., 2016).

Classification

Most of the bacteriocins are small, heat stable, cationic, amphiphilic and membrane permeabilizing peptides (Mokoena, 2017). Bacteriocin is classified into four classes on the basis of its amino acid compositions, molecular mass, thermostability, broad spectrum, enzymatic susceptibility genetics, mode of action, producer strains and types of post translational modifications and sized (Kumariya et al., 2019; Negash and Tsehai, 2020; Zimina et al., 2020). Four classes are recognized with their subclasses namely: Class I which represents as lantibiotics, small peptides (< 5 kDa) such as nisin, subtilin, mutacin, etc. (Meade et al., 2020), Class II is non-lantibiotics, small peptides (< 10 kDa) such as enterocins, pediocins, etc. (Song et al., 2014), Class III is large (> 30 kDa) heat liable protein such as helveticin, caseicin, etc. (Mokoena et al., 2017) and Class IV is bacteriocins with non-protein moieties mostly lipids or carbohydrate parts such as plantaricin S, leuconocin S, etc. (Simons et al., 2020).

Class I bacteriocin—Lantibiotics

Lantibiotics are post-translationally modified protein, small peptides (< 5 kDa) make up of 19–50 amino acids, heat stable and containing unusual amino acids residues called lanthionine, β-methyllanthionine, dehydroalanine, labyrinthin and dehydrobutyrine (Kumariya et al., 2019). Based on the biosynthetic enzymes within the operon coding for the production, modification and transport of the lantibiotic, class I bacteriocin is further divided into 5 sub-classes namely: Class Ia (Lantibiotics), Class Ib (labyrinthopeptins), Class1c (Sanctibiotics/Lanthipeptides), ClassId (Lanthipeptides containing Zinc-binding motif) and Class Ie (Lexapeptide) (Simons et al., 2020). Class Ia lantibiotics usually undergo dehydration of threonine and serine and cyclization, which are mainly carried out by the enzyme encoded genes LanB and LanC (Lagedroste et al., 2020). This leads to the formation of screw shaped, elongated, amphipathic peptide molecules producing voltage dependent pores by binding to the receptor lipid II and having mode of action as membrane permeabilization (Dickman et al., 2019). Nisin is one of the most common groups with unique amino acid such as lanthionine and β-methyllanthionine produced by Lactococcus lactis (Saraiva et al., 2020). Class Ib lantibiotics contain enzyme that encoded for lanM gene having the properties of both dehydration and cyclization that lead to the formation of globular, anionic or neutral peptide molecules (Repka et al., 2017). It is a modified post-translational, carbacyclic lantibiotics containing labionin and labyrinthin (Lagedroste et al., 2020). Mutacin II and labyrinthopeptin A1 are produced by Streptococcus mutans T8 (Férir et al., 2013). Class Ic bacteriocin is a sulphur to alpha carbon-containing antibiotics, referred as lanthipeptides or sactibiotics (Alvarez-Sieiro et al., 2016). The formation of lanthipeptides is catalysed by tri-functional enzymes encoded genes, lanKC (that contain lyase, kinase and cyclase) (Repka et al., 2017). Class Id is the lantibiotics such as streptocollin that contains zinc-binding motif in the cyclization domain, produced by Strepotomyces collinus Ti365 (Iftime et al., 2015). Class V is also known as lexapeptide, a novel F42OH2-dependent reductase that catalyse the reduction of dehydroalanine to install D-Ala, is produced by actinomycetes and cyanobacteria (Xu et al., 2020a, 2020b).

Gene organisation, biosynthesis and mode of actions of Lantibiotics

Many genes are involved which form an operon cluster for active production of bacteriocins (Noda et al., 2018). Operons of the lantibiotics have: a) structural genes which consist of leader peptide attach toward the core peptide (LanA); b) biosynthetic enzyme encoding genes: post translation modification of the peptides (LanBC), transporter protein (LanT) in which ABC transporter helps to attach the modification machinery to the cytoplasmic membrane, protease (helps to release the core peptide from leader sequence making peptide active) (LanP); c) immunity proteins: immunity of the peptide (LanIFEG); and d) regulatory unit: regulates the production of peptide (Lan RK) (Lagedroste et al., 2020; Sandiford et al., 2020). Schematic organization of gene clusters involved in the biosynthesis of Class I lantibiotics is shown in Fig. 2. The structural gene and its surrounding regions divergently transcribe and contribute toward the production of lantibiotics, its extracellular translocation, regulation of the lantibiotics synthesis and the immunity of the producers (Lajis et al., 2020; Simons et al., 2020).

Fig. 2.

Schematic representation of gene clusters involved in the biosynthesis of different class of bacteriocins (Class I, Class II, Class III and Class IV). Different colour indicates the different functions of gene responsible for the biosynthesis of lantibiotics: orange arrows indicate the modification gene, purple arrows for transport and processing, green arrows for immunity, blue arrows for regulatory, yellow arrows for structural genes and white and pink arrows is the gene whose function is not known yet

(adopted from Halami, 2019; Iftime et al., 2015; Mathur et al., 2017; Xin et al., 2016; Xu et al., 2020a, 2020b)

Lantibiotics are expressed as pre-propeptides (N-terminal leader sequence and a C-terminal pro-peptide) and post-translationally modified, then biosynthesis of the lantibiotics begin with the enzymatic dehydration of serine and threonine residues that lead to the formation of unusual amino acids 2,3-dehydrobutyrine (Dhb) and 2,3- dehydroalanine (Dha) (Repka et al., 2017). In these amino acids, the thiol group of neighbouring cysteine residue is added, which form the lanthionine from Dha and methyllanthionine from Dhb residues (Jones et al., 2020). The stable thioether-based intramolecular rings determined the 3-D structure of the peptides, which are very much needed for the biological activity (Li et al., 2019). NisB and NisC are modification enzymes that dehydrate and cyclize the pro-peptide and NisT are ABC transporter, which help in the translocation of the pre-peptide into the extracellular space (Repka et al., 2017). Subsequently NisP is the protease that cleaves the leader peptide thereby releasing the active form (mature) nisin, which possess immunity system for the nisA (Montalbán-López et al., 2018). Nisin consists of two component regulation systems: NisK (histidine kinase) and NisR (response regulator), which are responsible for the up-regulation for the nisin gene thereby activating the nisin (Geiger et al., 2017). However, in case of subtilin, the AbrB repressor allows the low-expression of the SpaRK (two-component regulatory system) (Geiger et al., 2017). Subtilin auto induces histidine kinase SpaK, which phosphorylates the SpaR (Response regulator) (Chakicherla et al., 2009), thereby upregulating the transcription of subtilin biosynthesis and immunity genes (Spieß et al., 2015).

Most of the lantibiotics produced by Gram-positive bacteria are active against other species of Gram-positive bacteria (Acedo et al., 2018). Lantibiotics of Gram-positive bacteria are less effective against Gram-negative bacteria which might be due to the outer membrane of Gram-negative bacteria not penetrable by the peptides (Halami, 2019). Lantibiotics are able to destabilize the membrane by forming a pore that will lead to misbalance of the membrane potential which ultimately results in leakage of small metabolites and termination of cellular biosynthetic processes (Barbour et al., 2020). The main target for the cationic bacteriocins is the cytoplasmic membrane of the bacterial cells, having anionic property which is composed of lipopolysaccharide (LPS), cardiolipin (CL), lipotheichoic acid (LTA), phosphatidylethanolamine (PE) phosphatidylglycerol (PG) (Kumariya et al., 2019). Lantibiotics act upon the cytoplasmic membrane of the bacterial cells called membrane bound peptidoglycan precursor lipid II, which will lead to the dissipation of the proton motive force (PMF), which is made up of chemical component and an electrical component (Niamah, 2018). In the membrane, this will drive the synthesis of ATP and lead to the accumulation of ions and other metabolites through PMF-driven transport systems (Pokhrel et al., 2019). Lantibiotics actions will collapse the PMF, resulting in cell death by the stoppage of energy-requiring reactions (Kumariya et al., 2019).

Class II bacteriocin: non lantibiotics

Class II bacteriocins are small (< 10 kDa) peptides, non-modified, ribosomally synthesis peptides, heat stable, glycine content and called non-lantibiotics and further classified into four subtypes listed, which include: Class IIa, Class IIb, Class IIc and Class IId (Cao et al., 2019; Cui et al., 2021; Negash and Tsehai, 2020). Class IIa is a small thermostable peptide, containing N-terminal conservative sequence YGNGV, having mode of action as membrane permeabilization by binding to the receptors mannose permease, and having a strong inhibitory effect on Listeria (Colombo et al., 2018; Wang et al., 2019). These Class IIa bacteriocin is produced by strains of Lactobacillus, Pediococcus, Enterococcus and Leuconostoc (Chen et al., 2018; Hammi et al., 2019; Zommiti et al., 2018). Pediocin PA-1, Lakacin, Leucocin A, Garviecin LG34, Sakacin, Enterocin, Acidocin A, Bavaricin A are the examples of Class IIa (Chen et al., 2018; Cui et al., 2021; Hashim et al., 2019; Hwang et al., 2018; Kassaa et al., 2019; Liu et al., 2019). Class IIb bacteriocin is the unmodified, two-peptides bacteriocins, having the structure of GxxxG motifs (Kumariya et al., 2019; Wang et al., 2019). These include two different peptides which are much needed to form an active poration complex for the membrane permeabilization by binding toward the receptors UppP (undecaprenyl pyrophosphate phosphatise) (Kasuga et al., 2019). Plantaricin JK, lactococcins, lactococin and enterocinX are the common Class IIb bacteriocins produced by Lactiplantibacillus plantarum (= Lactobacillus plantarum), Lactococcus lactis, Lactobacillus johnsonii (Butorac et al., 2020; Xu et al., 2019). Class IIc bacteriocin is a circular bacteriocin in which N and C-termini are covalently linked, having membrane permeabilization as a mode of action in which ABC transporter is the binding receptors. Acidocin B, Gassericin A, Enterocin AS-48, Gassericin A and Garvicin ML are the Class IIc and are produced by Lactobacillus acidophilus, Lb. gasseri, Lb. garvieae, Enterococcus faecalis and Lactococcus lactis (Alizadeh, et al., 2020; Baños et al., 2019; Chi et al., 2018; Garcia-Gutierrez et al., 2020). Class IId bacteriocin is linear, unmodified, leaderless and non-pediocin like bacteriocins having membrane permeabilization as a mode of action by binding to the receptors Metallope-ptidase (Alizadeh et al., 2020). Class IId bacteriocin includes Lacticin Z, Carnobacteriocin A, Enterocin Q, Bactofencin A, LsbB, Weissellicin 110, Thuricin S and Lactococcin A produced by Ligilactobacillus salivarius (= Lactobacillus salivarius), Carnobacterium piscicola, Enterococcus faecium L50 and Weissella cibaria 110 (Nazari and Smith, 2020; O’Connor et al., 2018; Zhang et al., 2019; Zimina et al., 2020).

Gene organisation, biosynthesis and mode of actions of class II bacteriocins

Many genes are involved, which include bacteriocin precursor peptide, immunity protein, ABC transporter complex and two or more operons for the biosynthesis of Class II bacteriocin (Kumariya et al., 2019). In each subtype, the organization of gene is different, such as the location of ABC transporter gene, GG-motifs containing peptides and also the gene encoding an accessory factor (Wang et al., 2019). For example, Pediocin PA-1 consists of four genes pedA, pedI, pedT and pedD (Fig. 2) encoding for pro-peptide, immunity protein, transport and processing. During the export of the peptides, the signal peptide is cleaved off at the C-terminal side of the two glycine residues, which is done by the ATP-binding cassette (Cao et al., 2019). Similarly, plantaricin has a similar operon structure like pediocin PA-1 (Bédard et al., 2018). The class II bacteriocin produces an induction factor that help in activating the transcription of the regulatory genes, hereby play an important role in the biosynthesis of class II bacteriocins (Colombo et al., 2018).

Mode of action of Class II bacteriocins vary from species to species, also it has been reported that it displays narrow spectrum when compared with nisin (Class Ia bacteriocin). Listeria strains are the common pathogens targeted by the class II bacteriocin (Colombo et al., 2018). Many studies have found that Leuconostoc, Lactococcus, Enterococcus, Staphylococcus, Lactobacillus, Pediococcus, Carnobacterium, Micrococcus, Streptococcus, Clostridium and Bacillus and many more are sensitive toward the class II bacteriocin (Negash and Tsehai, 2020). Class II bacteriocin binds to the cytoplasmic membrane thereby inserting the peptides into the membrane, which may cause the formation of pore complex that permeabilizes the membrane leading to the disruption of the PMF which finally cause cell death (Kumariya et al., 2019; Wang et al., 2019).

Class III and IV bacteriocins

Class III bacteriocins are large molecules (> 30 kDa), sensitive to heat and are classified based on the hydrolase activity (Mokoena, 2017). Class IIIa bacteriocins have hydrolase like activity and called as bacteriolysins and Class IIIb bacteriocin is without hydrolase activity and named as non-lytic (Wang et al., 2019). Lysostaphin and Zoocin A are the examples of Class IIIa produced by Staphylococcus simulans and Lactobacillus sp. (Simons et al., 2020). Enterolysin A and Helveticin J, Helveticin M and Lactococcin 972 are the common examples of ClassIIIb bacteriocin and are synthesised by Enterococcus, Lactobacillus and Lactococcus (Li et al., 2021; Meng et al., 2021; Stoyancheva, 2020). Mode of action of Class IIIa bacteriocin is to permeabilize the membrane and to form pores (Simons et al., 2020). Class IV bacteriocins are very complex, circular bacteriocins made up of lipid or carbohydrate moieties. Some examples of Class IV bacteriocins are PediocinN5p, lactocin27 and Enterocin Gr17, Lacstrepsin and Lactocin 27 and are produced by Pediococcus pentosaceus, Lactobacillus helveticus LP27 and LS18, Enterococcus faecalis Gr17 and Streptococcus lactis (Gutiérrez-Cortés et al., 2018; Liu et al., 2019).

Gene organisation, biosynthesis and mode of actions of Class III and IV bacteriocin

Many genes are involved for the production of bacteriocin but in case of Class III bacteriocin, gene involved in the production shows a great diversity in its structural gene, immunity gene, regulatory gene, transport and processing genes (Sun et al., 2018). Figure 2 depicts the gene organization of Class IIIa and Class IIIb bacteriocin, and, the arrangement of gene in Class IV bacteriocin. The main target of Class III bacteriocin in both Gram-negative and Gram-positive bacteria is bacterial cytoplasmic membrane (Negash and Tsehai, 2020). This Class III bacteriocin depolarizes the cell membrane, permits leakage of ATP, thereby increases the membrane impairment (Sun et al., 2018). Class IV circular bacteriocin is ribosomally synthesized peptides, which is post translationally modified in such a way that the first and last amino acids of the peptide (mature) are covalently bonded corresponding to the head to tail ligation (Meade et al., 2020; Vezina et al., 2020). Class IV circular bacteriocin has an inhibitory effect against Gram-positive as well as Gram-negative species (Perez et al., 2018; Wang et al., 2019).

Bacteriocin-producing LAB in fermented food

Bacteriocins produced by the Gram-positive bacteria especially LAB isolated from fermented foods (Goel et al., 2020; Liu et al., 2019; Pei et al., 2020) have been concerning more interest among the researchers because of their biosafety and industrial application most importantly for food preservation (Johnson et al., 2019). Many researchers have isolated the class I bacteriocin such as nisin, subtilin, lactocin as well as class II bacteriocins such as plantaricin, enterocin, pentocin, pediocin, etc. from fermented foods (Table 1). Bacteriocin is reported from many fermented vegetable products such as Korean kimchi (Lee et al., 2002; Liu et al., 2017), Chinese fermented vegetable products (Garcia-Gonzalez et al., 2021; Ullah et al., 2017). Levilactobacillus brevis (= Lactobacillus brevis), Lacticaseibacillus casei (= Lactobacillus casei), Lactiplantibacillus plantarum and Leuconostoc spp. are the most common LAB strains isolated from the fermented vegetables and pickles, which produce class I bacteriocin like subtilin and lactocin as well as class II bacteriocins like plantaricin, leucocin, garviecin (Islam et al., 2020; Kim et al., 2019; Lv et al., 2018; Shi et al., 2016; Zhao et al., 2016). Nisin-like bacteriocin is produced by Lactococcus lactis subsp. lactis A164 isolated from Korean kimchi (Choi et al., 2000). Proline-based cyclic dipeptides is produced by Leuconostoc mesenteroides LBP-K06, isolated from kimchi, which have antimicrobial activities against multidrug-resistant bacteria (Liu et al., 2017).

Table 1.

Bacteriocin-producing lactic acid bacteria isolated from ethnic fermented foods

Producer strain	Bacteriocin	Class	Fermented foods (Country)	Spectrum	References
Lactiplantibacillus plantarum strain DHCU70 and Lactiplantibacillus plantarum strain DKP1	Plantaricin	Class IIa bacteriocin	Dahi fermented yogurt-like milk product and Kinema, fermented soybean food (India)	Kocuria rhizophila ATCC 9341	Goel et al. (2020)
Enterococcus faecalis Gr17	Enterocin P	class IIa	Suan yu, fermented vegetable pickle (China)	Listeria monocytogenes, Escherichia coli, Staphyococcusaureus, Bacillus subtilis, B. cereus	Liu et al. (2019)
Lactobacillus spp.	Bacteriocin	–	Fermented vegetable cucumber & carrot (Bangladesh)	E. coli, S. aureus, B. cereus, B. subtilis, Acetobacter, E. coli, E. fecalis, Salmonella typhi	Islam et al. (2020)
Levilactobacillus brevis DF01 and Pediococcus acidilactici K10	BLIS (bacteriocin-like inhibitory substance)	–	Kimchi (Korean fermented vegetable)	S. typhimurium and E. coli	Kim et al. (2019)
Lactococcus lactis KC24	Bacteriocin KC24	–		Listeria monocytogenes	Han et al. (2013)
Lacticaseibacillus rhamnosus 1.0320	Bacteriocin 1.0320	–	Koumiss (Russian fermented milk-kefir grain)	E. coli UB1005	Xu et al. (2020a, 2020b)
Lactiplantibacillus plantarum MXG-68	Plantaricin MXG-68	Class IIa		L. monocytogenes ATCC15313, B. ereus ATCC11788, E. coli ATCC25922, S. typhimurium ATCC14028	Man et al. (2019)
Lactiplantibacillus plantarum B21	Plantacyclin B21AG	Class II	Nem chua (Vietnamese sausage)	L. monocytogene, Clostridium perfringens	Golneshin et al. (2020)
Limosilactobacillus fermentum BZ532	Bacteriocin LF-BZ532	Class II	Bozai (Chinese fermented cereal-based beverage)	E. coli k-12, S. aureus ATCC6538, Salmonella sp. D104	Rasheed et al. (2020)
Lactobacillus pentosus DZ35	Pentocin DZ1 and pentocin DZ2	Class II	Pickles and dried cured meat	S. aureus, E. coli	Yi et al. (2020)
Lactiplantibacillus plantarum	Bacteriocin- SLG10	Class IId	Kombucha (Chinese fermented tea)	S. aureus	Pei et al. (2020)
Lacticaseibacillus casei KLDS 1.0338	Bacteriocin		Sourdough (European and American fermented sour bread)	S. aureus, Penicillium sp.	Ma et al. (2020)
Lactiplantibacillus plantarum LPL-1	Plantaricin LPL-1	Class IIa	Sausage	L. monocytogenes	Zhang et al. (2020)
Lactiplantibacillus plantarum	Bacteriocin-M1-UVs300			L. monocytogenes, S. aureus, Micrococcus luteus, B. subtilis, Streptococcus thermophiles, Salmonella paratyphi, Shigella dysenteriae, E. coli	An et al. (2017)
Lactococcus lactis	Nisin Z	Class I		Micrococcus luteus	Saraiva et al. (2020)
Enterococcus hirae ST57ACC	Enterocin	–	Brazilian artisanal cheese	–	Cavicchioli et al. (2019)
Pediococcus acidilactici	BLIS	–	Gappal (fermented milk-millet mixture product of Burkina Faso)	E. faecalis ATCC 19,433, M. luteus ATCC 49,732, S. aureus ATCC 2523, L. monocytogenes, B. megaterium, B. sphaericus and B. cereus	Tankoano et al. (2019)
Pediococcus pentosaceus LU11 and Lactiplantibacillus plantarum LS6	Pediocin and Plantaricin	Class IIa	Tungtap (Indian fermented fish) and Tungrymbai (Indian fermented soybean food)	Streptococcus pyogenes, E. faecalis, E. coli, Klebsiella pneumoniae, B. cereus	Biswas et al. (2017)
Lacticaseibacillus casei	LiN333	–	Jiangshui cai (Chinese fermented vegetable)	E. coli, S. aureus	Ullah et al. (2017)
Lactobacillus coryniformis MXJ 32	Lactocin MXJ 32A	Class I		E. coli, S. aureus, Salmonella sp., L. monocytogenes, Cronobacter sakazakii	Lü et al. (2014)
Enterococcus faecalis KT11	Bacteriocin KT11	–	Kargı tulum cheese (Turkish goat’ milk cheese)	P. aeruginosa, B. cereus, M. luteus	Abanoz and Kunduhoglu (2018)
Lactiplantibacillus plantarum J23	Bacteriocin Lac-B23	–	Chinese fermented milk products	L. monocytogenes	Zhang et al. (2018)
Lactiplantibacillus plantarum LPL-1	Plantaricin LPL-1	Class IIa	Chinese fermented fish products	E. coli, Salmonella sp.	Wang et al. (2018)
Lactobacillus alimentarius FM-MM4	Lactocin MM4	Class II	Nanx wudl (Chinese fermented meat)	E. coli and Salmonella	Hu et al. (2017)
Lactiplantibacillus plantarum Q7	Plantaricin Q7	–	Yak yogurt	Ps. fluorescens AS1.1802	Liu et al. (2016)
Lactiplantibacillus plantarum	Plantaricin	Class II	Bekasam (Indonesian fermented meat), tapai (Indonesian fermented rice) and tempoyak (Indonesian fermented durian food)	B. subtilis, Pseudomonas aeroginosa	Sogandi et al. (2019)
Lactococcus lactis subsp. Lactis	Nisin Z	Class I	Charqui (Brazilian fermented meat)	L. monocytogenes ScottA	Biscola et al. (2013)
Leuconostoc mesenteroides K7	Leucocin K7	Class IIa	Fermented pickle	L. Monocytogenes	Shi et al. (2016)
Lactiplantibacillus plantarum ZJ5	Plantaricin ZJ5	Class II	Fermented mustard	S. aureus	Song et al. (2014)
Lactiplantibacillus plantarum JLA-9,	Plantaricin JLA-9	Class II	Suan-tsai (Chinese fermented cabbage)	B. cereus	Zhao et al. (2016)
Lactiplantibacillus plantarum DL3	Plantaricin DL3			Pseudomonas aeruginosa	Lv et al. (2018)
Lactiplantibacillus plantarum KLDS1.0391	Plantaricin MG	Class II	Jiaoke (Chinese fermented milk product)	L. monocytogenes, S. aureus, Sal. typhimurium, E. coli	Gong et al. (2010)
Lactococcus lactis subsp. lactis MA23	Bacteriocin MA23	–	Boza (African fermented cereal-based beverage)	Gram-positive bacteria	Akkoc et al. (2011)
Lactococcus lactis subsp. lactis BZ	Lactococcin BZ	Class I		Lactobacillus, Enterococcus, Leuconostocs, Listeria, Bacillus, Enterobacter, Escherichia, Rhodococcus, Salmonella, Yersinia, Citrobacter spp.	Şahingil et al. (2011)
Streptococcus infantarius subsp. Infantarius	Bacteriocin	–	Suusac (African fermented camel-milk product)	Other LAB, Listeria	Jans et al. (2012)
Lactococcus garvieae BCC 43,578	Garvieacin Q	Class IIa	Nham (Thai fermented pork meat)	E. faecium, L. monocytogenes	Tosukhowong et al. (2012)
Weissella hellenica BCC 7293	Bacteriocin 7293A and 7293B	–		L. monocytogenes, S. aureus, Sal. typhimurium, E. coli, Pseudomonas aeruginosa, Aeromonas hydrophila	Woraprayote et al. (2015)
Lactobacillus sakei D98	Sakacin D98a, sakacin D98b and sakacin D98c	Class IIa	Shubo/moto (Japanese starter for sake production)	B. circulans, L. innocua, L. monocytogenes, E.faecalis, L. sakei ssp. sakei	Sawa et al. (2013)
Lactococcus garvieae LG34	Garviecin LG34	Class IIa	Chinese fermented cucumber	L. delbruleckii subsp. bulgaricus, L. acidophilus, S. aureus, L. monocytogenes, E. coli, Shigella flexneri, L. plantarum L8, L. delbruleckii subsp. delbrueckii, S. thermophilus, Sarcina flava, Salmonella thyphimurium	Gao et al. (2015)

Lactococcus lactis subsp. lactis strain 63

Lactococcus lactis subsp. lactis strain 63, isolated from Indian dairy products, produces bacteriocin that inhibits Listeria monocytogenes, Bacillus cereus, E. coli, Klebsiella, Enterobacter, Citrobacter, Proteus and Serratia strains (Goyal et al., 2018). Several LAB species isolated from Romanian traditional fermented fruits and vegetables have antimicrobial activity against L. monocytogenes, E. coli, Salmonella, and Bacillus (Gaggia et al., 2011).

Fermented milk and milk products are considered as the vital sources for isolation of bacteriocin producing LAB. Lactiplantibacillus plantarum strain DHCU70 isolated from dahi, a yogurt-like Indian fermented milk product produces class II preservative called plantaricin and found to exhibit cell-wall inhibiting mechanism to the target cells (Goel et al., 2020). Lactobacillus rhamnosus and Lactiplantibacillu plantarum, isolated from koumiss a fermented milk-kefir grain beverage, have shown the antimicrobial effect against E-coli and Listeria monocytogenes due to production of bacteriocin such as plantaricin (Man et al., 2019; Xu et al., 2020a, 2020b). Bacteriocin-producing LAB have been reported from yogurt and cheese (Gutiérrez-Cortés et al., 2018; Niederhäusern et al., 2020; Silva et al., 2018), fermented milk products of Egypt (Refay et al., 2020), African fermented milk (Maleke et al., 2021). Bacteriocin-producing LAB isolated from many fermented cereal-based products may be utilized for the bio-preservation of foods (Ma et al., 2020; Pei et al., 2020; Rasheed et al., 2020). Enterocin P producing Enterococcus faecalis Gr17, isolated from the traditional Chinese fermented fish called suan yu, shows the antimicrobial effects against the L. momocytogenes, E. coli, S. aureus and B. cereus (Liu et al., 2019).

Ethnic fermented foods dock several species of functional and beneficial microorganisms, which produce bacteriocin as one of the secondary metabolites. Due to the differences in its gene coding for the production, secretion and immunity, each bacteriocins have unique structures and different modes of activity thus making them ideal candidate having different properties. Thereby, many investigators shifted their focus on bacteriocin from food preservation to the treatment of infection and antibiotic-resistant diseases causing bacteria. Also with the latest technique in gene mining, synthesis and protein expression study, it became promising to look forward with the novel bacteriocin having advanced applications.

Declarations

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.