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CwrA, a gene that specifically responds to cell wall damage in Staphylococcus aureus

Balibar, Carl and Shen, Xiaoyu and Mcguire, Dorothy and Yu, Donghui and Mckenney, David and Tao, Jianshi (2010) CwrA, a gene that specifically responds to cell wall damage in Staphylococcus aureus. Microbiology, 156 (Pt 5). pp. 1372-1383.

Abstract

Transcriptional profiling data accumulated in recent years for the clinically relevant pathogen Staphylococcus aureus have established a cell wall stress stimulon, which is comprised of a coordinately regulated set of genes which are upregulated in response to blockage of cell wall biogenesis. In particular, the expression of cwrA (SA2343, N315 notation), which encodes a putative 63-amino acid polypeptide with unknown biological function, increases over 100-fold in response to cell wall inhibition. Herein we seek to understand the biological role this gene plays in S. aureus. CwrA was found to be robustly induced by all cell wall targeting antibiotics tested – vancomycin, oxacillin, penicillin G, phosphomycin, imipenem, hymeglusin, and bacitracin – but not by antibiotics with other mechanisms of action, including ciprofloxacin, erythromycin, chloramphenicol, triclosan, rifampin, novobiocin, and carbonyl cyanide 3-chlorophenylhydrazone. Although a cwrA S. aureus strain had no appreciable shift in MICs for cell wall targeting antibiotics, the knockout was shown to have reduced cell wall integrity in a variety of other assays. Additionally, the gene was shown to be important for virulence in a mouse sepsis model of infection.

Item Type: Article
Keywords: CCCP; carbonyl cyanide m-chlorophenylhydrazone; RLU; relative light units; TEM; transmission electron microscopy; UPP; undecaprenyl pyrophosphate;
Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/2303

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