Faculty Collaboration Database

Bacteriocin production augments niche competition by enterococci in the mammalian gastrointestinal tract. Nature 2015 Oct 29;526(7575):719-22

Date

10/20/2015

Pubmed ID

26479034

Pubmed Central ID

PMC4978352

DOI

10.1038/nature15524

Scopus ID

2-s2.0-84945964162 (requires institutional sign-in at Scopus site)   322 Citations

Abstract

Enterococcus faecalis is both a common commensal of the human gastrointestinal tract and a leading cause of hospital-acquired infections. Systemic infections with multidrug-resistant enterococci occur subsequent to gastrointestinal colonization. Preventing colonization by multidrug-resistant E. faecalis could therefore be a valuable approach towards limiting infection. However, little is known about the mechanisms E. faecalis uses to colonize and compete for stable gastrointestinal niches. Pheromone-responsive conjugative plasmids encoding bacteriocins are common among enterococcal strains and could modulate niche competition among enterococci or between enterococci and the intestinal microbiota. We developed a model of colonization of the mouse gut with E. faecalis, without disrupting the microbiota, to evaluate the role of the conjugative plasmid pPD1 expressing bacteriocin 21 (ref. 4) in enterococcal colonization. Here we show that E. faecalis harbouring pPD1 replaces indigenous enterococci and outcompetes E. faecalis lacking pPD1. Furthermore, in the intestine, pPD1 is transferred to other E. faecalis strains by conjugation, enhancing their survival. Colonization with an E. faecalis strain carrying a conjugation-defective pPD1 mutant subsequently resulted in clearance of vancomycin-resistant enterococci, without plasmid transfer. Therefore, bacteriocin expression by commensal bacteria can influence niche competition in the gastrointestinal tract, and bacteriocins, delivered by commensals that occupy a precise intestinal bacterial niche, may be an effective therapeutic approach to specifically eliminate intestinal colonization by multidrug-resistant bacteria, without profound disruption of the indigenous microbiota.

Author List

Kommineni S, Bretl DJ, Lam V, Chakraborty R, Hayward M, Simpson P, Cao Y, Bousounis P, Kristich CJ, Salzman NH

Authors

Christopher J. Kristich PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of Wisconsin
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Bacteriocins
Conjugation, Genetic
Disease Models, Animal
Drug Resistance, Multiple, Bacterial
Enterococcus faecalis
Gastrointestinal Tract
Gram-Positive Bacterial Infections
Male
Mice
Microbial Viability
Microbiota
Molecular Sequence Data
Mutation
Plasmids
Symbiosis
Vancomycin Resistance