Faculty Collaboration Database

A eukaryotic-type Ser/Thr kinase in Enterococcus faecalis mediates antimicrobial resistance and intestinal persistence. Proc Natl Acad Sci U S A 2007 Feb 27;104(9):3508-13

Date

03/16/2007

Pubmed ID

17360674

Pubmed Central ID

PMC1805595

DOI

10.1073/pnas.0608742104

Scopus ID

2-s2.0-33847675357 (requires institutional sign-in at Scopus site)   132 Citations

Abstract

Antibiotic-resistant enterococci are major causes of hospital-acquired infections. The emergence of Enterococcus faecalis as a significant nosocomial pathogen is a consequence of its inherent resistance to certain antibiotics and of its ability to survive and proliferate in the intestinal tract. Genetic determinants of E. faecalis conferring these properties are largely unknown. Here we show that PrkC, a one-component signaling protein containing a eukaryotic-type Ser/Thr kinase domain, modulates inherent antimicrobial resistance and intestinal persistence of E. faecalis. An E. faecalis mutant lacking PrkC grows at a wild-type rate in the absence of antimicrobial stress but exhibits enhanced sensitivity to cell-envelope-active compounds, including antibiotics that target cell-wall biogenesis and bile detergents. Consistent with its bile sensitivity, the mutant was also impaired at persistence in the intestine of mice. Thus, PrkC regulates key physiological processes in E. faecalis associated with its success as a nosocomial pathogen. The predicted domain architecture of PrkC comprises a cytoplasmic kinase domain separated by a transmembrane segment from extracellular domains thought to bind uncross-linked peptidoglycan, suggesting that PrkC is a transmembrane receptor that monitors the integrity of the E. faecalis cell wall and mediates adaptive responses to maintain cell-wall integrity. Given its role in modulating traits of E. faecalis important for its ability to cause nosocomial infections, we suggest that the one-component signaling protein PrkC represents an attractive target for the development of novel therapies to prevent infections by antibiotic-resistant enterococci.

Author List

Kristich CJ, Wells CL, Dunny GM

Author

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

Animals
Anti-Bacterial Agents
Bacterial Proteins
Drug Resistance, Bacterial
Enterococcus faecalis
Female
Intestines
Mice
Microbial Sensitivity Tests
Microscopy, Electron, Scanning
Mutation
Protein Structure, Tertiary