title: Requirement of the CroRS Two-Component System for Resistance to Cell Wall-Targeting Antimicrobials in Enterococcus faecium.
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 inEnterococcus faecalisHere, we identify and characterize an orthologous two-component system found inEnterococcus faeciumthat is functionally equivalent to the CroRS system ofE. faecalisDeletion ofcroRSinE. faeciumresulted in marked susceptibility to cell wall-targeting agents including cephalosporins and bacitracin, as well as moderate susceptibility to ampicillin and vancomycin. As inE. faecalis, exposure to bacitracin and vancomycin stimulates signaling through the CroRS system inE. faeciumMoreover, the CroRS system is critical inE. faeciumfor 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.
authors.affiliation: Department of Microbiology and Immunology, Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Kellogg
authors.affiliation: Department of Microbiology and Immunology, Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Little
authors.affiliation: Department of Microbiology and Immunology, Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Hoff
authors.affiliation: Department of Microbiology and Immunology, Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA ckristich@mcw.edu.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kristich
mesh_terms: D000595:Amino Acid Sequence; D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001414:Bacitracin / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D002473:Cell Wall / Q000187:drug effects*; D002511:Cephalosporins / Q000494:pharmacology; D013293:Enterococcus faecalis / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D016984:Enterococcus faecium / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D008826:Microbial Sensitivity Tests; D011494:Protein Kinases / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D014640:Vancomycin / Q000494:pharmacology; D018440:beta-Lactam Resistance / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002511:Cephalosporins; D015534:Trans-Activators; D001414:Bacitracin; D014640:Vancomycin; D000667:Ampicillin; D011494:Protein Kinases
keywords: antibiotic resistance; enterococcus; two-component regulatory systems