| The CroRS two-component regulatory system is required for intrinsic beta-lactam resistance in Enterococcus faecalis. | |
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MedLine Citation:
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PMID: 14645279 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Enterococcus faecalis produces a specific penicillin-binding protein (PBP5) that mediates high-level resistance to the cephalosporin class of beta-lactam antibiotics. Deletion of a locus encoding a previously uncharacterized two-component regulatory system of E. faecalis (croRS) led to a 4,000-fold reduction in the MIC of the expanded-spectrum cephalosporin ceftriaxone. The cytoplasmic domain of the sensor kinase (CroS) was purified and shown to catalyze ATP-dependent autophosphorylation followed by transfer of the phosphate to the mated response regulator (CroR). The croR and croS genes were cotranscribed from a promoter (croRp) located in the rrnC-croR intergenic region. A putative seryl-tRNA synthetase gene (serS) located immediately downstream from croS did not appear to be a target of CroRS regulation or to play a role in ceftriaxone resistance. A plasmid-borne croRp-lacZ fusion was trans-activated by the CroRS system in response to the presence of ceftriaxone in the culture medium. The fusion was also induced by representatives of other classes of beta-lactam antibiotics and by inhibitors of early and late steps of peptidoglycan synthesis. The croRS null mutant produced PBP5, and expression of an additional copy of pbp5 under the control of a heterologous promoter did not restore ceftriaxone resistance. Deletion of croRS was not associated with any defect in the synthesis of the nucleotide precursor UDP-MurNAc-pentapeptide or of the D-Ala(4)-->L-Ala-L-Ala-Lys(3) peptidoglycan cross-bridge. Thus, the croRS mutant was susceptible to ceftriaxone despite the production of PBP5 and the synthesis of wild-type peptidoglycan precursors. These observations constitute the first description of regulatory genes essential for PBP5-mediated beta-lactam resistance in enterococci. |
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Authors:
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Yannick Comenge; Richard Quintiliani; Ling Li; Lionnel Dubost; Jean-Paul Brouard; Jean-Emmanuel Hugonnet; Michel Arthur |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of bacteriology Volume: 185 ISSN: 0021-9193 ISO Abbreviation: J. Bacteriol. Publication Date: 2003 Dec |
Date Detail:
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Created Date: 2003-12-03 Completed Date: 2004-01-07 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 2985120R Medline TA: J Bacteriol Country: United States |
Other Details:
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Languages: eng Pagination: 7184-92 Citation Subset: IM |
Affiliation:
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INSERM E0004-LRMA, UFR Broussais-Hôtel Dieu, Université Paris VI, 75270 Paris, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anti-Bacterial Agents
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pharmacology Bacterial Proteins / chemistry, genetics, metabolism Carbohydrate Sequence Ceftriaxone / pharmacology Chromosome Mapping Cytoplasm / metabolism Enterococcus faecalis / drug effects*, genetics*, metabolism Gene Deletion Molecular Sequence Data Peptidoglycan / metabolism Promoter Regions, Genetic RNA, Messenger beta-Lactam Resistance / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Anti-Bacterial Agents; 0/Bacterial Proteins; 0/Peptidoglycan; 0/RNA, Messenger; 73384-59-5/Ceftriaxone |
| Comments/Corrections | |
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