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Bacteriocins: History
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Subjects: Microbiology
Contributor: Juan Carlos Hernandez Gonzalez

Las bacteriocinas son péptidos antimicrobianos termoestables, sintetizados ribosómicamente. Tanto las bacterias grampositivas como las gramnegativas y las arqueas liberan péptidos antimicrobianos extracelularmente en las fases de crecimiento exponencial tardía a estacionaria temprana.

  • bacteriocins
  • antimicrobials
  • lactic acid bacteria
  • probiotics
  • immunomodulation
  • veterinary medicine

1. Introducción

An essential attribute of bacteriocins is the antimicrobial activity against different bacteria, fungi, parasites, viruses, and even against natural resistant structures, such as bacterial biofilms [1][2][3][4]. Lactic acid bacteria (LAB) are a heterogeneous group of Gram-positive bacteria. They are classified according to glucose fermentation characteristics, cell morphology, capacity to utilize sugars, and optimum growth temperature range [5]. Thus, this classification system recognized a core group consisting of four genera: Lactobacillus, Pediococcus, Leucononstoc, and Streptococcus [6]. Molecular biological methods have increased the number of genera, including the following: Aerococcus, Alloiococcus, Carnobacterium, Dolosigranulum, Enterococcus, Lactococcus, Lactosphaera, Melissococus, Oenococcus, Tetragenococcus, Vagococcus, and Weissella [5][7]. Various studies have shown that LAB inhibit pathogenic microorganisms growth, degrade mycotoxins, and have a probiotic effect [5]. LAB are found abundantly in nature and symbiotically interact with higher organisms. They have been isolated from several sources, including dairy products, meat, fruits, and vegetables. They can also be found in mucous membranes of the respiratory, intestinal, and other anatomical sites of man and animals, even in plants, wastewater, soil, and manure [8]. Bacteriocins have been used as food preservatives, due to their ability to inhibit microorganisms potentially harmful to human health. They are safe for consumption and do not alter the quality and safety of food [9][10]. Furthermore, bacteriocins from LAB have had a significant development in other fields, such as in the cosmetic industry and human and veterinary medicine [11][12]. In animal production, bacteriocin-producing bacteria have been used as probiotics in the diet or drinking water of pigs, poultry, and fish, which has increased their growth rate [13][14].

2. The Probiotic Activity of LAB Bacteriocins

Oral administration of purified or semipurified bacteriocins has been shown to have limitations. Digestive enzymes can degrade bacteriocins, and bacteriocins can adhere to food particles or diffuse through digestion, among others [15]. The protection of bacteriocins in capsules or nanocapsules can be an alternative to prevent enzymatic degradation and avoid various doses and high concentrations of bacteriocins [16]. Thus, the most efficient method for taking advantage of bacteriocins in the digestive tract includes bacteriocin-producing LAB as probiotics. This strategy favors the colonization of bacteria in the gastrointestinal tract, and bacteriocins can be produced in situ [17]. There are multiple benefits of using LAB in place of antibiotics or growth promoters. These include modulation of microbiota, improving the intestinal barrier function and digestion, preventing the colonization of enteric pathogens, and stimulating the immune system [14][18][19][20]. However, studies showed that E. faecium LMG 30881, a producer of enterocin B in the canine diet, caused unfavorable effects, such as runny stools, higher Gram-negative bacterial counts, and lower hemoglobin concentrations [21][22]. The use of bacteriocin-producing LAB probiotic in dogs requires more research, since no further work has been generated in this regard to date. In healthy pigs, it has been shown that some LAB of the gastrointestinal tract prevents villous atrophy of the post-weaning stage, promotes the maturation of gastrointestinal lymphoid tissue, and has immunomodulatory activity. Oral administration of the probiotic Lactobacillus salivarius B1 (isolated from healthy piglets) in newborn piglets showed that the probiotic bacteria colonized the duodenal mucosa and increased the height of the villi, which improved absorption and promoted the integrity of the intestinal barrier. Interestingly, L. salivarius increased the expression of porcine beta-defensin 2 (pBD-2), an antimicrobial peptide produced by host cells. Continuous probiotic administration caused a considerable increase in the production of pBD-2, which could even be detected in the saliva of piglets [23]. In the duodenum and ileum, the number of intraepithelial lymphocytes, plasma cells that produce IgA, and the synthesis of Toll-Like Receptor-2 (TLR-2) increased. In the ileum, interleukin-6 (IL-6), a cytokine that promotes the differentiation and proliferation of B lymphocytes, was increased [19].

These studies suggest that the immunomodulatory effects of L. salivarius B1 are due to bacteriocins [24]. L. salivarius UCC118 (isolated from the human intestinal microbiota) produces the bacteriocin Abp118. This antimicrobial peptide has been shown to have activity against L. monocytogenes [25][26]. L. salivarius UCC 118, as a probiotic added to the diet of pigs after weaning, showed that LAB colonized the ileum and caused a significant decrease in spirochetes (Treponema), considered to be opportunistic pathogens of pigs [27]. Rustic or native animals on farms can be a natural source of bacteriocins-producing probiotics. A study has shown that miniature piglets from Congjiang (a breed of pig native to China) had higher resistance to stress-induced diarrhea during early weaning due to gut microbiota. In the feces of miniature piglets, a higher population of Lactobacillus gasseri LA39 and Lactobacillus frumenti, producers of the bacteriocin gassericin, was found. This study also demonstrated an increase in the signaling pathway involved in protein expression (NHE3, SLC5A1, DRA, and PAT1) associated with intestinal absorption. Gassericin decreased the expression of proteins related to intestinal secretion (NKCC1, CFTR, CaCC1). These bacteria could be transplanted into commercial crossbred piglets before weaning and prevent diarrhea after weaning. This study provides a strategy for the possible prevention of diarrhea in pigs and even other mammals [28]. There are reports of more than 30 LAB as probiotics that inhibit the growth of pathogenic microorganisms in birds; however, their mode of action remain poorly understood [29][30][31]. LAB as probiotics in poultry has been used to control experimental coccidial infection, endemic in the commercial broiler industry. Studies on the inclusion of multispecies probiotics (E. faecium, Bifidobacterium animalis, and L. salivarius) in food or water have shown that the colonization of LAB in the intestine causes a coccidiostatic effect on Eimeria spp. In addition, the probiotic prevented intestinal damage without affecting body weight gain values. On the other hand, there were high probiotic LAB amounts in intestinal microbiota, while coliform and C. perfringens were lower than the control group [32]. The multispecies probiotic for commercial use can be integrated into chicken microbiota early in ovo and for one day of hatching. These bacteria increased protection against Eimeria spp. and commercial vaccine-administered response, at the same time [33][34]. The species of genera Enterococcus spp., as a probiotic for use in the poultry industry, has been shown to produce enterocin A, B, P, and L50 and bacteriocin-like inhibitory substances that are not identified currently. These bacteriocins have demonstrated antimicrobial activity in vitro against pathogenic bacterial C. perfringens, S. aureus, Salmonella Heidelberg, and L. monocytogenes [35][36].

3. Conclusions

Bacteriocins are a powerful weapon that can be exploited in veterinary medicine. The administration of these antimicrobial peptides in domestic animals eliminates potentially pathogenic undesirable microorganisms without causing cytotoxicity on cells or tissues. Interestingly, it does not generate resistance to antibiotics, and resistance to bacteriocins is minimal. Bacteriocins are analogous and synergistic when combined with antiseptics, antibiotics, and ionophores, showing greater potency than antimicrobial peptides from eukaryotic cells. In addition, these combinations can reduce resistance to bacteriocins.

The potential use of bacteriocins alone or along with microbicidal agents has potential therapeutic actions in periodontal disease and mastitis in dairy cows, prevents postoperative infections in fractures, and coccidiostats and improves productive parameters in substitution of antibiotics as growth promoters. In animal nutrition, bacteriocins reduce cholesterol and triglycerides, thus improving the quality of the meat as a final product. LAB colonize the intestinal mucosa and produce bacteriocins in situ. LAB and their bacteriocins promote the integrity of the intestinal barrier, eliminate bacteria that interfere with the use of nutrients, and stimulate the expression of proteins associated with the absorption of intestinal fluid. This finding suggests that they can be used as probiotics in poultry and monogastric animals. Furthermore, these bioactive peptides have a role in the immune response as immunomodulators. Bacteriocins modulate the expression of anti-inflammatory cytokines to promote the repair of cell damage. Some of them are potent inducers of antimicrobial peptides in eukaryotic cells, which improve the innate immune response against pathogens. However, the bacteriocins produced by virulent bacteria can be a virulence factor, promoting a proinflammatory cytokine profile, which favors infection in lymphoid cells and organs. Little is known about the immunomodulatory effects of bacteriocins in animals. More studies are required to fully understand the role of bacteriocins on the innate and adaptive response that could contribute to the control or resolution of infections or diseases. LAB bacteriocins are projected as new antimicrobials that could be targeted or stabilized by nanotechnology and prevent enzymatic digestion. In addition, more research is required on modifications that could increase the potency of bacteriocins. The benefits of bacteriocins shown in vitro and in vivo assays provide support for developing and researching clinical trials in the different areas of veterinary medical therapeutics.

This entry is adapted from the peer-reviewed paper 10.3390/ani11040979

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