Anti-adhesion and Anti-inflammatory Potential of the Leaderless Class IIb Bacteriocin Enterocin DD14.

In this study, we investigate the interactions between the leaderless class IIb bacteriocin, enterocin DD14 (EntDD14), or the methicillin or the combination of these antibacterials, and two methicillin-resistant Staphylococcus aureus strains (MRSA-S1 and USA 300) which are respectively a clinical strain and a reference strain. The results obtained showed that EntDD14 alone or in combination with the antibiotic could significantly prevent the adhesion of these pathogenic bacteria to human cells. On the other hand, we investigated the anti-inflammatory effect of EntDD14 on the secretion of pro-inflammatory interleukins, including IL-6 and IL-8. The results show that EntDD14 is able to decrease significantly the secretion of both interleukins on Caco-2 cells following their treatments with lipopolysaccharides. These novel data provide insightful informations to support applications of bacteriocins as therapeutic agents capable as well to defeat pathogenic bacteria and concomitantly limit their inflammatory reactions.

Alginate Nanoparticles Enhance Anti-Clostridium perfringens Activity of the Leaderless Two-Peptide Enterocin DD14 and Affect Expression of Some Virulence Factors.

Here, we report a novel approach to improve the anti-Clostridium perfringens activity of the leaderless two-peptide enterocin 14 (EntDD14), produced by Enterococcus faecalis 14. This strategy consists of loading EntDD14 onto alginate nanoparticles (Alg NPs), which are made of a safe polymer. The resulting formulation (EntDD14/Alg NPs) was able to reduce up to four times the minimum inhibitory concentration (MIC) of EntDD14 against C. perfringens pathogenic strains isolated from a chicken affected by necrotic enteritis (NE). Interestingly, this formulation remained active under conditions mimicking the human and chicken gastric tract. Assays conducted to establish the impact of this formulation on the intestinal epithelial cell line Caco-2 and the human colorectal adenocarcinoma cell line HT29 revealed the absence of cytotoxicity of both free-EntDD14 and EntDD14 loaded onto the alginate nanoparticles (EntDD14/Alg NPs) against the aforementioned eukaryotic cells, after 24 h of contact. Notably, EntDD14 and EntDD14/Alg NPs, both at a sub-inhibitory concentration, affected the expression of genes coding for clostridial toxins such as toxin α, enteritis B-like toxin, collagen adhesion protein and thiol-activated cytolysin. Further, expression of these genes was significantly down-regulated following the addition of EntDD14/Alg NPs, but not affected upon addition of EntDD14 alone. This study revealed that adsorption of EntDD14 onto Alg NPs leads to a safe and active formulation (EntDD14/Alg NPs) capable of affecting the pathogenicity of C. perfringens. This formulation could therefore be used in the poultry industry as a novel approach to tackle NE.

Broadening and Enhancing Bacteriocins Activities by Association with Bioactive Substances.

Bacteriocins are antimicrobial peptides some of which are endowed with antiviral, anticancer and antibiofilm properties. These properties could be improved through synergistic interactions of these bacteriocins with other bioactive molecules such as antibiotics, phages, nanoparticles and essential oils. A number of studies are steadily reporting the effects of these combinations as new and potential therapeutic strategies in the future, as they may offer many incentives over existing therapies. In particular, bacteriocins can benefit from combination with nanoparticles which can improve their stability and solubility, and protect them from enzymatic degradation, reduce their interactions with other molecules and improve their bioavailability. Furthermore, the combination of bacteriocins with other antimicrobials is foreseen as a way to reduce the development of antibiotic resistance due to the involvement of several modes of action. Another relevant advantage of these synergistic combinations is that it decreases the concentration of each antimicrobial component, thereby reducing their side effects such as their toxicity. In addition, combination can extend the utility of bacteriocins as antiviral or anticancer agents. Thus, in this review, we report and discuss the synergistic effects of bacteriocin combinations as medicines, and also for other diverse applications including, antiviral, antispoilage, anticancer and antibiofilms.