ABSTRACT
In recent decades, bacteriocins have received substantial attention as antimicrobial compounds. Although bacteriocins have been predominantly exploited as food preservatives, they are now ...receiving increased attention as potential clinical antimicrobials and as possible immune-modulating agents. Infections caused by antibiotic-resistant bacteria have been declared as a global threat to public health. Bacteriocins represent a potential solution to this worldwide threat due to their broad- or narrow-spectrum activity against antibiotic-resistant bacteria. Notably, despite their role in food safety as natural alternatives to chemical preservatives, nisin remains the only bacteriocin legally approved by regulatory agencies as a food preservative. Moreover, insufficient data on the safety and toxicity of bacteriocins represent a barrier against the more widespread use of bacteriocins by the food and medical industry. Here, we focus on the most recent trends relating to the application of bacteriocins, their toxicity and impacts.
Antimicrobial activity, gastrointestinal bihaviour and toxicity of bacteriocins.
A wide variety of antimicrobial peptides produced by lactic acid bacteria (LAB) have been identified and studied in the last decades. Known as bacteriocins, these ribosomally synthesized peptides ...inhibit the growth of a wide range of bacterial species through numerous mechanisms and show a great variety of spectrum of activity. With their great potential as antimicrobial additives and alternatives to traditional antibiotics in food preservation and handling, animal production and in veterinary and medical medicine, the demand for bacteriocins is rapidly increasing. Bacteriocins are most often produced by fermentation but, in several cases, the low isolated yields and difficulties associated with their purification seriously limit their use on a large scale. Chemical synthesis has been proposed for their production and recent advances in peptide synthesis methodologies have allowed the preparation of several bacteriocins. Moreover, the significant cost reduction for peptide synthesis reagents and building blocks has made chemical synthesis of bacteriocins more attractive and competitive. From a protein engineering point of view, the chemical approach offers many advantages such as the possibility to rapidly perform amino acid substitution, use unnatural or modified residues, and make backbone and side chain modifications to improve potency, modify the activity spectrum or increase the stability of the targeted bacteriocin. This review summarized synthetic approaches that have been developed and used in recent years to allow the preparation of class IIa bacteriocins and
-linked glycopeptides from LAB. Synthetic strategies such as the use of pseudoprolines, backbone protecting groups, microwave irradiations, selective disulfide bridge formation and chemical ligations to prepare class II and
-glycosylsated bacteriocins are discussed.
The overuse and misuse of antibiotics has contributed to the rise and spread of multidrug-resistant bacteria. To address this global public health threat, many countries have restricted the use of ...antibiotics as growth promoters and promoted the development of alternatives to antibiotics in human and veterinary medicine and animal farming. In food-animal production, acidifiers, bacteriophages, enzymes, phytochemicals, probiotics, prebiotics, and antimicrobial peptides have shown hallmarks as alternatives to antibiotics. This review reports the current state of these alternatives as growth-promoting factors for poultry and swine production and describes their mode of action. Recent findings on their usefulness and the factors that presently hinder their broader use in animal food production are identified by SWOT (strength, weakness, opportunity, and threat) analysis. The potential for resistance development as well as co- and cross-resistance with currently used antibiotics is also discussed. Using predetermined keywords, we searched specialized databases including Scopus, Web of Science, and Google Scholar. Antibiotic resistance cannot be stopped, but its spreading can certainly be hindered or delayed with the development of more alternatives with innovative modes of action and a wise and careful use of antimicrobials in a One Health approach.
Multidrug-resistant
infections are a major threat to the poultry industry. Effective alternatives to antibiotics are urgently needed to prevent these infections and limit the spread of ...multidrug-resistant bacteria. The aim of the study was to produce by chemical synthesis a set of enterocins of different subgroups of class II bacteriocins and to compare their spectrum of inhibitory activity, either alone or in combination, against a panel of twenty
isolates. Enterocins A, P, SEK4 (class IIa bacteriocins), B (unsubgrouped class II bacteriocin), and L50 (class IId leaderless bacteriocin) were produced by microwave-assisted solid-phase peptide synthesis. Their antimicrobial activity was determined by agar well diffusion and microtitration methods against twenty
isolates and against other pathogens. The FIC
of different combinations of the selected enterocins was calculated in order to identify combinations with synergistic effects. The results showed that synthetic analogs of L50A and L50B were the most active against
. These peptides also showed the broadest spectrum of activity when tested against other non-clostridial indicator strains, including
, methicillin-resistant
,
,
,
,
, as well as Gram-negative bacteria (
and
), among others. The selected synthetic enterocins were combined on the basis of their different mechanisms of action, and all combinations tested showed synergy or partial synergy against
. In conclusion, because of their high activity against
and other pathogens, the use of synthetic enterocins alone or as a consortium can be a good alternative to the use of antibiotics in the poultry sector.
Bacteriocins are receiving increased attention as potent candidates in food preservation and medicine. Although the inhibitory activity of bacteriocins has been studied widely, little is known about ...their gastrointestinal stability and toxicity toward normal human cell lines. The aim of this study was to evaluate the gastrointestinal stability and activity of microcin J25, pediocin PA-1, bactofencin A and nisin using
models. In addition cytotoxicity and hemolytic activity of these bacteriocins were investigated on human epithelial colorectal adenocarcinoma cells (Caco-2) and rat erythrocytes, respectively. Pediocin PA-1, bactofencin A, and nisin were observed to lose their stability while passing through the gastrointestinal tract, while microcin J25 is only partially degraded. Besides, selected bacteriocins were not toxic to Caco-2 cells, and integrity of cell membrane was observed to remain unaffected in presence of these bacteriocins at concentrations up to 400 μg/mL. In hemolysis study, pediocin PA-1, bactofencin A, and nisin were observed to lyse rat erythrocytes at concentrations higher than 50 μg/mL, while microcin J25 showed no effect on these cells. According to data indicating gastrointestinal degradation and the absence of toxicity of pediocin PA-1, bactofencin A, and microcin J25 they could potentially be used in food or clinical applications.
Bacteria-derived natural antimicrobial compounds such as bacteriocins, reruterin, and organic acids have recently received substantial attention as food preservatives or therapeutic alternatives in ...human or animal sectors. This study aimed to evaluate the antimicrobial activity of different bacteria-derived antimicrobials, alone or in combination, against a large panel of Gram-negative and Gram-positive bacteria. Bacteriocins, including microcin J25, pediocin PA-1, nisin Z, and reuterin, were investigated alone or in combination with lactic acid and citric acid, using a checkerboard assay. Concentrations were selected based on predetermined MICs against Salmonella enterica subsp.
serovar Newport ATCC 6962 and Listeria ivanovii HPB28 as Gram-negative and Gram-positive indicator strains, respectively. The results demonstrated that the combination of microcin J25 + citric acid + lactic acid; microcin J25 + reuterin + citric acid; and microcin J25 + reuterin + lactic acid tested against
Newport ATCC 6962 showed synergistic effects (FIC index = 0.5). Moreover, a combination of pediocin PA-1 + citric acid + lactic acid; and reuterin + citric acid + lactic acid against
HPB28 showed a partially synergistic interactions (FIC index = 0.75). Nisin Z exerted a partially synergistic effect in combination with acids (FIC index = 0.625 -0.75), whereas when it was combined with reuterin or pediocin PA-1, it showed additive effects (FIC index = 1) against
HPB28. The inhibitory activity of synergetic consortia were tested against a large panel of Gram-positive and Gram-negative bacteria. According to our results, combining different antimicrobials with different mechanisms of action led to higher potency and a broad spectrum of inhibition, including multidrug-resistance pathogens.
Reuterin and bacteriocins, including microcin J25, pediocin PA-1, nisin were produced and purified with >90% purity. Using the broth-based checkerboard assay the interaction between these compounds (synergetic, additive, or antagonistic) was assessed. By combining different natural antimicrobials with different modes of action and structure (reuteirn, microcin J25, pediocin PA-1, and organic acids), we successfully developed five different synergetic consortia with improved antimicrobial activity and a broad spectrum of inhibition. These consortia were shown to be effective against a large panel of pathogenic and spoilage microorganisms as well as clinically important multidrug-resistance bacteria. Moreover, because the lower concentrations of bacteriocins and reuterin are used in the synergetic consortia, there is a limited risk of toxicity and resistance development for these compounds.
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•Reuterin (3-hyrdoxypropionaldehyde (3-HPA)) is a highly potent metabolite of Lactobacillus reuteri.•Reuterin is highly stable in gastrointestinal condition.•Human colorectal ...adenocarcinoma cells’ viability and membrane integrity remained unaltered by reuterin.•No significant hemolytic activity was detected.•Reuterin is a promising therapeutic and/or food preservative.
Reuterin (3-hyrdoxypropionaldehyde (3-HPA)) is a highly potent metabolite of L. reuteri, which has applications in food, health, and veterinary sectors. Similar to other natural antimicrobial compounds, the approval of reuterin as a bio-preservative or therapeutic agent by regulatory agencies relies on sufficient data on its cytotoxicity and behavior in the gastrointestinal environment. Although the antimicrobial activity of reuterin has been broadly studied, its safety and toxicity are yet to be explored in detail. In this study, the stability and activity of reuterin were investigated in the gastrointestinal tract using in vitro models simulating gastrointestinal conditions. In addition, hemolytic activity and in vitro cytotoxicity of reuterin were evaluated by neutral red assay and lactate dehydrogenase (LDH) colorimetric assay using the same cell line. Activity of reuterin was observed to be stable during gastrointestinal transit. Viability and membrane integrity of cells remained unaltered by reuterin up to 1080 mM concentration. Furthermore, no hemolysis was observed in blood cells exposed to 270 mM reuterin. This study provides unique and highly relevant in vitro data regarding gastrointestinal behavior and toxicity of reuterin. In conclusion, the current study indicates that within a certain concentration range, reuterin can be safely used in bio-preservation and therapeutics applications. However, further in vivo studies are required to confirm these findings.
reaction: see text We report highly efficient two-step procedures for the synthesis of 1,3-oxazole-, thiazole-, and imidazole-containing peptides on solid phase from dipeptides composed of C-terminal ...threonine, serine, cysteine, or diaminopropionic acid by using different cyclodehydration procedures followed or preceded by oxidation. The methods are compatible with Fmoc solid-phase peptide synthesis conditions and with N-Fmoc, N-Boc, N-Cbz, and N-Alloc protecting groups.
Glial cells have emerged as key players in the central control of energy balance and etiology of obesity. Astrocytes play a central role in neural communication via the release of gliotransmitters. ...Acyl-CoA binding protein (ACBP)-derived endozepines are secreted peptides that modulate the GABAA receptor. In the hypothalamus, ACBP is enriched in arcuate nucleus (ARC) astrocytes, ependymocytes and tanycytes. Central administration of the endozepine octadecaneuropeptide (ODN) reduces feeding and improves glucose tolerance, yet the contribution of endogenous ACBP in energy homeostasis is unknown. We demonstrated that ACBP deletion in GFAP+ astrocytes, but not in Nkx2.1-lineage neural cells, promoted diet-induced hyperphagia and obesity in both male and female mice, an effect prevented by viral rescue of ACBP in ARC astrocytes. ACBP-astrocytes were observed in apposition with proopiomelanocortin (POMC) neurons and ODN selectively activated POMC neurons through the ODN-GPCR but not GABAA, and supressed feeding while increasing carbohydrate utilization via the melanocortin system. Similarly, ACBP overexpression in ARC astrocytes reduced feeding and weight gain. Finally, the ODN-GPCR agonist decreased feeding and promoted weight loss in ob/ob mice. These findings uncover ACBP as an ARC gliopeptide playing a key role in energy balance control and exerting strong anorectic effects via the central melanocortin system.
In this study, we first report characterization of collagencin, an antimicrobial peptide identified from fish collagen hydrolysate. The peptide completely inhibited the growth of Staphylococcus ...aureus at 1.88 mM. Although non-toxic up to 470 μM, collagencin was hemolytic at higher concentrations. The secondary structure of collagencin was mainly composed by β-sheet and β-turn as determined by CD measurements and molecular dynamics. The peptide is likely to form β-sheet structure under hydrophobic environments and interacts with both anionic (phosphatidylglycerol) and zwitterionic (phosphoethanolamine and phosphatidylcholine) lipids as shown with CD spectroscopy and molecular dynamics. The peptide formed several hydrogen bonds with both POPG and POPE lipids and remained at membrane–water interface, suggesting that collagencin antibacterial action follows a carpet mechanism. Collagenous fish wastes could be processed by enzymatic hydrolysis and transformed into products of high value having functional or biological properties. Marine collagens are a promising source of antimicrobial peptides with new implications in food safety and human health.
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•Collagencin, an antibacterial (G+ & G-) peptide identified from fish collagen hydrolysate.•The peptide completely inhibited the growth of S. aureus at 1.88 mM and non-toxic at 470 μM.•The secondary structure was mainly composed by β-sheet and turn as determined by CD and MD.•Collagencin interacts with both anionic and zwitterionic lipids as shown with CD and MD.•Collagencin antibacterial action probably follows a carpet mechanism.
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