cwrA, a gene that specifically responds to cell wall damage in Staphylococcus aureus.
Transcriptional profiling data accumulated in recent years for the clinically relevant pathogen Staphylococcus aureus have established a cell wall stress stimulon, which comprises a coordinately regulated set of genes that 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 of unknown biological function, increases over 100-fold in response to cell wall inhibition. Herein, we seek to understand the biological role that 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, rifampicin, novobiocin and carbonyl cyanide 3-chlorophenylhydrazone. Although a DeltacwrA 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.
Balibar
Carl J
CJ
Department of Infectious Diseases, Novartis Institutes for BioMedical Research, 500 Technology Square, Cambridge, MA 02139, USA.
Shen
Xiaoyu
X
Department of Infectious Diseases, Novartis Institutes for BioMedical Research, 500 Technology Square, Cambridge, MA 02139, USA.
McGuire
Dorothy
D
Department of Infectious Diseases, Novartis Institutes for BioMedical Research, 500 Technology Square, Cambridge, MA 02139, USA.
Yu
Donghui
D
Department of Infectious Diseases, Novartis Institutes for BioMedical Research, 500 Technology Square, Cambridge, MA 02139, USA.
McKenney
David
D
Department of Infectious Diseases, Novartis Institutes for BioMedical Research, 500 Technology Square, Cambridge, MA 02139, USA.
Tao
Jianshi
J
Department of Infectious Diseases, Novartis Institutes for BioMedical Research, 500 Technology Square, Cambridge, MA 02139, USA.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001433:Bacteriolysis; D002473:Cell Wall / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D017930:Genes, Reporter; D008248:Lysostaphin / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D018805:Sepsis / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure; D014774:Virulence
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C551261:cwrA protein, Staphylococcus aureus; D008248:Lysostaphin