MurAA is required for intrinsic cephalosporin resistance of Enterococcus faecalis. Antimicrob Agents Chemother 2012 May;56(5):2443-51
Date
02/01/2012Pubmed ID
22290954Pubmed Central ID
PMC3346666DOI
10.1128/AAC.05984-11Scopus ID
2-s2.0-84858689036 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
Enterococcus faecalis is a low-GC Gram-positive bacterium that is intrinsically resistant to cephalosporins, antibiotics that target cell wall biosynthesis. To probe the mechanistic basis for intrinsic resistance, a library of transposon mutants was screened to identify E. faecalis strains that are highly susceptible to ceftriaxone, revealing a transposon mutant with a disruption in murAA. murAA is predicted to encode a UDP-N-acetylglucosamine 1-carboxyvinyl transferase that catalyzes the first committed step in peptidoglycan synthesis: phosphoenolpyruvate (PEP)-dependent conversion of UDP-N-acetylglucosamine to UDP-N-acetylglucosamine-enolpyruvate. In-frame deletion of murAA, but not its homolog in the E. faecalis genome (murAB), led to increased susceptibility of E. faecalis to cephalosporins. Furthermore, expression of murAA enhanced cephalosporin resistance in an E. faecalis mutant lacking IreK (formerly PrkC), a key kinase required for cephalosporin resistance. Further genetic analysis revealed that MurAA catalytic activity is necessary but not sufficient for this role. Collectively, our data indicate that MurAA and MurAB have distinct roles in E. faecalis physiology and suggest that MurAA possesses a unique property or activity that enables it to enhance intrinsic resistance of E. faecalis to cephalosporins.
Author List
Vesić 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
Alkyl and Aryl TransferasesBacterial Proteins
Ceftriaxone
Cephalosporin Resistance
DNA Transposable Elements
Enterococcus faecalis
Escherichia coli
Gene Deletion
Gram-Positive Bacterial Infections
Humans
Isoenzymes
Microbial Sensitivity Tests
Mutation
Phosphotransferases
Plasmids
Transformation, Bacterial
