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Requirement of the CroRS Two-Component System for Resistance to Cell Wall-Targeting Antimicrobials in Enterococcus faecium. Antimicrob Agents Chemother 2017 May;61(5)

Date

02/23/2017

Pubmed ID

28223383

Pubmed Central ID

PMC5404561

DOI

10.1128/AAC.02461-16

Scopus ID

2-s2.0-85018165537 (requires institutional sign-in at Scopus site)   40 Citations

Abstract

Enterococci are serious opportunistic pathogens that are resistant to many cell wall-targeting antibiotics. The CroRS two-component signaling system responds to antibiotic-mediated cell wall stress and is critical for resistance to cell wall-targeting antibiotics in Enterococcus faecalis Here, we identify and characterize an orthologous two-component system found in Enterococcus faecium that is functionally equivalent to the CroRS system of E. faecalis Deletion of croRS in E. faecium resulted in marked susceptibility to cell wall-targeting agents including cephalosporins and bacitracin, as well as moderate susceptibility to ampicillin and vancomycin. As in E. faecalis, exposure to bacitracin and vancomycin stimulates signaling through the CroRS system in E. faecium Moreover, the CroRS system is critical in E. faecium for enhanced beta-lactam resistance mediated by overexpression of Pbp5. Expression of a Pbp5 variant that confers enhanced beta-lactam resistance cannot overcome the requirement for CroRS function. Thus, the CroRS system is a conserved signaling system that responds to cell wall stress to promote intrinsic resistance to important cell wall-targeting antibiotics in clinically relevant enterococci.

Author List

Kellogg SL, Little JL, Hoff JS, Kristich CJ

Authors

Jessica Hoff PhD Assistant Professor in the Pathology department at Medical College of Wisconsin
Christopher J. Kristich PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin




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

Amino Acid Sequence
Ampicillin
Anti-Bacterial Agents
Bacitracin
Bacterial Proteins
Cell Wall
Cephalosporins
Enterococcus faecalis
Enterococcus faecium
Gene Deletion
Microbial Sensitivity Tests
Protein Kinases
Signal Transduction
Trans-Activators
Vancomycin
beta-Lactam Resistance