Modulators of Enterococcus faecalis Cell Envelope Integrity and Antimicrobial Resistance Influence Stable Colonization of the Mammalian Gastrointestinal Tract. Infect Immun 2018 Jan;86(1)
Date
10/19/2017Pubmed ID
29038125Pubmed Central ID
PMC5736811DOI
10.1128/IAI.00381-17Scopus ID
2-s2.0-85039561569 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
The Gram-positive bacterium Enterococcus faecalis is both a colonizer of the gastrointestinal tract (GIT) and an agent of serious nosocomial infections. Although it is typically required for pathogenesis, GIT colonization by E. faecalis is poorly understood. E. faecalis tolerates high concentrations of GIT antimicrobials, like cholate and lysozyme, leading us to hypothesize that resistance to intestinal antimicrobials is essential for long-term GIT colonization. Analyses of E. faecalis mutants exhibiting defects in antimicrobial resistance revealed that IreK, a determinant of envelope integrity and antimicrobial resistance, is required for long-term GIT colonization. IreK is a member of the PASTA kinase protein family, bacterial transmembrane signaling proteins implicated in the regulation of cell wall homeostasis. Among several determinants of cholate and lysozyme resistance in E. faecalis, IreK was the only one found to be required for intestinal colonization, emphasizing the importance of this protein to enterococcal adaptation to the GIT. By studying ΔireK suppressor mutants that recovered the ability to colonize the GIT, we identified two conserved enterococcal proteins (OG1RF_11271 and OG1RF_11272) that function antagonistically to IreK and interfere with cell envelope integrity, antimicrobial resistance, and GIT colonization. Our data suggest that IreK, through its kinase activity, inhibits the actions of these proteins. IreK, OG1RF_11271, and OG1RF_11272 are found in all enterococci, suggesting that their effect on GIT colonization is universal across enterococci. Thus, we have defined conserved genes in the enterococcal core genome that influence GIT colonization through their effect on enterococcal envelope integrity and antimicrobial resistance.
Author List
Banla IL, Kommineni S, Hayward M, Rodrigues M, Palmer KL, Salzman NH, Kristich CJAuthors
Christopher J. Kristich PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinNita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAnti-Bacterial Agents
Bacterial Proteins
Cell Membrane
Cell Wall
Conserved Sequence
Drug Resistance, Bacterial
Enterococcus faecalis
Gastrointestinal Tract
Genome, Bacterial
Gram-Positive Bacterial Infections
Male
Mammals
Mice
Mice, Inbred C57BL
Microbial Sensitivity Tests
Signal Transduction
