Oxidative stress enhances cephalosporin resistance of Enterococcus faecalis through activation of a two-component signaling system. Antimicrob Agents Chemother 2015 Jan;59(1):159-69
Date
10/22/2014Pubmed ID
25331701Pubmed Central ID
PMC4291345DOI
10.1128/AAC.03984-14Scopus ID
2-s2.0-84920163536 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
Enterococcus faecalis is a low-GC Gram-positive bacterium, a normal resident of the gastrointestinal (GI) tract, and an important hospital-acquired pathogen. An important risk factor for hospital-acquired enterococcal infections is prior therapy with broad-spectrum cephalosporins, antibiotics that impair cell wall biosynthesis by inhibiting peptidoglycan cross-linking. Enterococci are intrinsically resistant to cephalosporins; however, environmental factors that modulate cephalosporin resistance have not been described. While searching for the genetic determinants of cephalosporin resistance in E. faecalis, we unexpectedly discovered that oxidative stress, whether from external sources or derived from endogenous metabolism, drives enhanced intrinsic resistance to cephalosporins. A particular source of oxidative stress, H2O2, activates signaling through the CroR-CroS two-component signaling system, a known determinant of cephalosporin resistance in E. faecalis. We find that CroR-CroS is required for adaptation to H2O2 stress and that H2O2 potentiates the activities of cephalosporins against E. faecalis when the CroR-CroS signaling system is nonfunctional. Rather than directly detecting H2O2, our data suggest that the CroR-CroS system responds to cell envelope damage caused by H2O2 exposure in order to promote cell envelope repair and enhanced cephalosporin resistance.
Author List
Djorić D, Kristich CJAuthors
Dusanka Djoric Research Scientist I in the Microbiology and Immunology department at Medical College of WisconsinChristopher 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
Anti-Bacterial AgentsCell Wall
Cephalosporins
Drug Resistance, Bacterial
Enterococcus faecalis
Gastrointestinal Tract
Hydrogen Peroxide
Microbial Sensitivity Tests
Oxidative Stress
Sequence Deletion
Signal Transduction
