Mutations in the β subunit of RNA polymerase alter intrinsic cephalosporin resistance in Enterococci. Antimicrob Agents Chemother 2012 Apr;56(4):2022-7
Date
02/01/2012Pubmed ID
22290974Pubmed Central ID
PMC3318385DOI
10.1128/AAC.06077-11Scopus ID
2-s2.0-84858667570 (requires institutional sign-in at Scopus site) 29 CitationsAbstract
As major causes of hospital-acquired infections, antibiotic-resistant enterococci are a serious public health concern. Enterococci are intrinsically resistant to many cephalosporin antibiotics, a trait that enables proliferation in patients undergoing cephalosporin therapy. Although a few genetic determinants of cephalosporin resistance in enterococci have been described, overall, many questions remain about the underlying genetic and biochemical basis for cephalosporin resistance. Here we describe an unexpected effect of specific mutations in the β subunit of RNA polymerase (RNAP) on intrinsic cephalosporin resistance in enterococci. We found that RNAP mutants, selected initially on the basis of their ability to provide resistance to rifampin, resulted in allele-specific alterations of the intrinsic resistance of enterococci toward expanded- and broad-spectrum cephalosporins. These mutations did not affect resistance toward a diverse collection of other antibiotics that target a range of alternative cellular processes. We propose that the RNAP mutations identified here lead to alterations in transcription of as-yet-unknown genes that are critical for cellular adaption to cephalosporin stress.
Author List
Kristich CJ, Little JLAuthor
Christopher J. Kristich PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antitubercular AgentsCephalosporin Resistance
Culture Media
DNA-Directed RNA Polymerases
Enterococcus
Genetic Linkage
Microbial Sensitivity Tests
Mutation
Plasmids
Rifampin
