Capacity of Human Nisin- and Pediocin-Producing Lactic Acid Bacteria To Reduce Intestinal Colonization by Vancomycin-Resistant Enterococci

Abstract

This study demonstrated the capacity of bacteriocin-producing lactic acid bacteria (LAB) to reduce intestinal colonization by vancomycin-resistant enterococci (VRE) in a mouse model. Lactococcus lactis MM19 and Pediococcus acidilactici MM33 are bacteriocin producers isolated from human feces. The bacteriocin secreted by P. acidilactici is identical to pediocin PA-1/AcH, while PCR analysis demonstrated that L. lactis harbors the nisin Z gene. LAB were acid and bile tolerant when assayed under simulated gastrointestinal conditions. A well diffusion assay using supernatants from LAB demonstrated strong activity against a clinical isolate of VRE. A first in vivo study was done using C57BL/6 mice that received daily intragastric doses of L. lactis MM19, P. acidilactici MM33, P. acidilactici MM33A (a pediocin mutant that had lost its ability to produce pediocin), or phosphate-buffered saline (PBS) for 18 days. This study showed that L. lactis and P. acidilactici MM33A increased the concentrations of total LAB and anaerobes while P. acidilactici MM33 decreased the Enterobacteriaceae populations. A second in vivo study was done using VRE-colonized mice that received the same inocula as those in the previous study for 16 days. In L. lactis-fed mice, fecal VRE levels 1.73 and 2.50 log 10 CFU/g lower than those in the PBS group were observed at 1 and 3 days postinfection. In the P. acidilactici MM33-fed mice, no reduction was observed at 1 day postinfection but a reduction of 1.85 log 10 CFU/g was measured at 3 days postinfection. Levels of VRE in both groups of mice treated with bacteriocin-producing LAB were undetectable at 6 days postinfection. No significant difference in mice fed the pediocin-negative strain compared to the control group was observed. This is the first demonstration that human L. lactis and P. acidilactici nisin-and pediocin-producing strains can reduce VRE intestinal colonization.

Modulation of the gut microbiota by prebiotic fibres and bacteriocins

“…In the gut, bacteriocins may help the producer to survive and colonize, and inhibit the closely related competitive strains or pathogens, as well as influence the immune system of the host through their impact on gut microbial populations [80,81]. For instance, a Lactobacillus salivarius strain producing salivaricin P becomes predominant in porcine ileum when administered in combination with other probiotic strains that do not produce bacteriocins [82].…”

“…Antagonistic activity of the bacteriocin producers against a number of pathogenic or antibiotic-resistant bacterial strains in the gut has been a major focus of gut microbiota studies. Several LAB bacteriocins and/or bacteriocin-producing LAB have been shown to inhibit pathogens such as Listeria monocytogenes [83,84], Clostridium difficile [85–87], Staphylococcus aureus [88] and even Salmonella enteritidis [89], Some bacteriocin producers have also been reported to eliminate multidrug- or vancomycin-resistant enterococci [81,90]. Therefore, the production of bacteriocins may contribute to the beneficial activities in the gut.…”

Bacteriocin Production: a Probiotic Trait?

“…The inhibition of the pathogen was shown to be the direct result of the production of the two-peptide bacteriocin Abp118, as it was demonstrated that a non-bacteriocin-producing isogenic derivative failed to protect mice from infection. Similarly, the bacteriocinproducing human isolates P. acidilactici MM33 and L. lactis MM19 were shown to reduce vancomycin-resistant enterococci (VRE) populations in vivo (41). P. acidilactici MM33 produces the bacteriocin pediocin PA-1/AcH, while L. lactis MM19 produces the bacteriocin nisin Z.…”

Bacteriocin-producing strains of Lactobacillus plantarum inhibit adhesion of Staphylococcus aureus to extracellular matrix: quantitative insight and implications in antibacterial therapy

“…Based on this premise, probiotic LAB have been positioned in the vanguard of healthcare applications. Probiotic LAB can prevent pathogen colonization in the intestine by occupying sites and producing bacteriocins and other metabolites (Gopal et al, 2001;Lee et al, 2003;Millette et al, 2008;O'Shea et al, 2012). Several reports describe the beneficial effects of Lactobacillus species on the gastrointestinal tract (Bernbom et al, 2009;Guarner & Malagelada, 2003;O'Callaghan et al, 2012;Walter, 2008).…”