Bacteriocins: Classification, synthesis, mechanism of action and resistance development in food spoilage causing bacteria
Graphical abstract
Introduction
Food spoiling bacteria are threats to food quality and etiological agents for several pathologies - some debilitating and some fatal [1]. If pathogens such as neurotoxin-elaborating Clostridium botulinum [2], Listeria monocytogenes [3], Enterococcus [4], Streptococcus, Staphylococcus, Bacillus, Escherichia coli gain access to human tissues, they cause inflammatory disease, respiratory infection, systemic infection, intestinal disorder to cancer.
As the detrimental effects of chemical preservatives are coming forth, consumers are demanding safe and natural preservatives – the biopreservatives. Biopreservation is a natural means of preservation, involving the use of micro-organisms or their natural products [5]. Among other micro-organisms, lactic acid bacteria (LAB) have a major potential for use in biopreservation, as it produces an array of active antimicrobial substances like organic acids, hydrogen peroxide, bacteriocins etc. [6].
Bacteriocins are ribosomally-synthesized secreted anti-microbial peptides (AMP) of length 20-60 amino acids, cationic and hydrophobic, capable of inhibiting both food spoilage/pathogenic bacteria from both Gram-negative and Gram-positive group, thus provide a new strategy to combat them [[7], [8], [9]]. Among these, nisin, an AMP produced by LAB such as Lactococcus lactis, has been granted “generally regarded as safe” (GRAS) status for certain applications by Food and Drug Administration (FDA) [10]. Nisin is found to inhibit the germination of C. botulinum spores in cheese spreads, among other foods [11]. Pediocin is another AMP produced by Pediococcus sp [12]. A commercial preparation of pediocin PA-1 by Pediococcus acidilactici known as Alta™ 2341 has potential to extend the shelf life of a variety of ready-to-eat products, particularly by inhibiting the growth of L. monocytogenes [13]. Some other bacteriocins include subtilin, lichenicidin, cinnamycin, actagardine, epidermin, lacticin, carnobacteriocin, piscicolin, divergicin, mutacin, mundticin, mesenterocin, enterocin, sakacin, leucocin, curvacin, enterocin, lysostaphin, duramycin, brevinin, ruminococcin, curvaticin, and columbicin.
Bacteriocins are toxic to the producing bacteria as well, but by a suite of immunity proteins, they protect themselves [14]. Genes encoding bacteriocins, set of immunity proteins and other accessory proteins are arranged in an operon clusters that reside either in genome, plasmids or other mobile genetic elements. These operons, in general, are inducible and require secretion and extracellular accumulation of peptides for induction [15].
The sensitivity of microbes to bacteriocins is due to their interaction with bacterial cell surface and cell membrane. Cell permeabilization and pore formation is a major mechanism by which bacteriocins attack the target bacteria [16]. However, reports of resistance development by several food-spoilage/pathogenic bacteria against bacteriocins like nisin and pediocin have implied that increased resistance may compromise the potential role of these antimicrobial peptides in biopreservation [17]. If bacteriocins were rendered ineffective, it will be a huge problem for food sector. So, the mechanism of bacteriocin function and its degradation needs to be understood in order to tackle the resistance problem.
Since bacterial membrane surface charge and membrane fluidity are the two bacterial properties exploited by bacteriocins during the attack, manipulation in these properties renders the bacteriocins ineffective, resulting in bacteriocins resistance [16,18]. However, many studies have shown that the bacteriocins resistance can be overcome by using the combination of different bacteriocins [19] and/or bacteriocins and other antimicrobial compounds [20]. Also, potency of bacteriocins can be increased by bioengineering. Since unlike antibiotics, bacteriocins are ribosomally-synthesized peptides, thus can by bioengineered at specific amino acid residues to make them more effective against the food-spoilage bacteria [21]. Approaches that have been tried to mitigate the bacteriocin resistance are discussed in detail later.
This review discusses the classification, synthesis and mechanism of action of bacteriocins with emphasis on the different resistance mechanisms adopted by different food spoilage bacteria against bacteriocins.
Section snippets
Classification of bacteriocins
Bacteriocins were initially classified into four classes [22]. However, the fourth class of bacteriocins, consisting of large complexes with carbohydrate or lipid moieties, has been aborted and were named as bacteriolysins comprising of leuconocin S and lactocin 27 [23]. Thus, bacteriocins are classified majorly into three classes [24].
Class I bacteriocins typically comprises of 19–50 amino acids and are extensively post-translationally modified resulting in the non-standard amino acids, such
Synthesis and mechanism of action of bacteriocins
The genes for the production of active bacteriocins are usually in operon clusters, harbored in the genome, plasmid, or other mobile genetic elements. Expression of these operons is inducible and requires the presence of auto-inducer peptides for the induction [35]. Expression is regulated often by two-component regulatory system [36,37] and in some cases by three-component regulatory system [[38], [39], [40]]. Nisin itself serves as an auto-inducer for its expression by activating
Mechanism of resistance development in bacteria against bacteriocins
All organisms have inherent tendency to adapt to the changing environment. Thus, target bacteria also develop components to resist these bacteriocins on persistent exposure, leading to bacteriocin resistance. Bacteriocins have been in use since several decades, and resistance development has been an old problem. Resistance in target bacteria is acquired through different mechanisms. Table 2 summarizes resistance developed in bacteria against several bacteriocins [[50], [51], [52], [53]].
The
Approaches to mitigate bacteriocin resistance
Prebiotic sorbitol has a positive influence on bacteriocin production from P. acidilactici LAB5 [83]. Bacteriocin alone might not be enough for containing food spoiling bacteria. Too much dosage of the bacteriocin can result in unspecific bactericidal effect and may be hazardous for the consumer. So, pairing bacteriocin with other antimicrobial agents is considered. In this regard, plant essential oils have shown promise [84]. Thyme, cumin, rosemary, basil, coriander, mint, sage, lavender,
Concluding remarks
Bacteriocins are the ‘offense and defense’ molecules for both GRAS-category as well as pathogenic bacteria. On being exposed to bacteriocins, pathogens also elaborate their own repertoire of bacteriocins. This warfare leads to the evolution of the bacteriocins to avoid stalemate and for survival. The pathogens secrete enzymes which can degrade the bacteriocins. However, effective a bacteriocin might be, in no time, the target bacteria will develop weapons to disarm it. Also, out of the
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