title: Pheromone killing of multidrug-resistant Enterococcus faecalis V583 by native commensal strains.
abstract: Multidrug-resistant Enterococcus faecalis possess numerous mobile elements that encode virulence and antibiotic resistance traits as well as new metabolic pathways, often constituting over one-quarter of the genome. It was of interest to determine how this large accretion of mobile elements affects competitive growth in the gastrointestinal (GI) tract consortium. We unexpectedly observed that the prototype clinical isolate strain V583 was actively killed by GI tract flora, whereas commensal enterococci flourished. It was found that killing of V583 resulted from lethal cross-talk between accumulated mobile elements and that this cross-talk was induced by a heptapeptide pheromone produced by native E. faecalis present in the fecal consortium. These results highlight two important aspects of the evolution of multidrug-resistant enterococci: (i) the accretion of mobile elements in E. faecalis V583 renders it incompatible with commensal strains, and (ii) because of this incompatibility, multidrug-resistant strains sharing features found in V583 cannot coexist with commensal strains. The accumulation of mobile elements in hospital isolates of enterococci can include those that are inherently incompatible with native flora, highlighting the importance of maintaining commensal populations as means of preventing colonization and subsequent infection by multidrug-resistant strains.
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114; Department of Microbiology and Immunobiology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114; michael_gilmore@meei.harvard.edu.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gilmore
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114; Department of Microbiology and Immunobiology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114;
authors.forename: Marcus
authors.initials: M
authors.lastname: Rauch
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114; Department of Microbiology and Immunobiology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114;
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Ramsey
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114; Department of Microbiology and Immunobiology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114;
authors.forename: Paul R
authors.initials: PR
authors.lastname: Himes
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045.
authors.forename: Sriram
authors.initials: S
authors.lastname: Varahan
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114; Department of Microbiology and Immunobiology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114;
authors.forename: Janet M
authors.initials: JM
authors.lastname: Manson
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114; Department of Microbiology and Immunobiology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114;
authors.forename: Francois
authors.initials: F
authors.lastname: Lebreton
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045.
authors.forename: Lynn Ernest
authors.initials: LE
authors.lastname: Hancock
mesh_terms: D024901:Drug Resistance, Multiple, Bacterial; D013293:Enterococcus faecalis / Q000187:drug effects*; D006801:Humans; D010675:Pheromones / Q000494:pharmacology*
chemical_list: D010675:Pheromones
keywords: Enterococcus; antibiotics; fitness cost; resistance; vancomycin