Two-component system VraSR positively modulates the regulation of cell-wall biosynthesis pathway in Staphylococcus aureus.
Kuroda, Makoto 1,*; Kuroda, Hiroko 1; Oshima, Taku 2; Takeuchi, Fumihiko 3,4; Mori, Hirotada 2; Hiramatsu, Keiichi 1
[Article]
Molecular Microbiology.
49(3):807-821, August 3, 2003.
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Summary: DNA microarray covering the whole genome of Staphylococcus aureus strain N315 was prepared to investigate transcription profiles. The microarray analyses revealed that vancomycin induces transcription of 139 genes. Forty-six genes among them failed to be induced in the vraSR null mutant KVR. Part of the genes regulated by VraSR system is associated with cell-wall biosynthesis, such as PBP2, SgtB and MurZ. Other cell-wall synthesis inhibitors also induced VraSR, suggesting that the sensor kinase VraS responds to the damage of cell-wall structure or inhibition of cell-wall biosynthesis. Additionally, the vraSR null mutants derived from hetero- and homo-methicillin-resistant S. aureus showed significant decrease of resistance against teicoplanin, [beta]-lactam, bacitracin and fosfomycin but not of D-cycloserine and levofloxacin. The observation strongly indicates that VraSR constitutes a positive regulator of cell-wall peptidoglycan synthesis, and that is deeply involved in the expression of [beta]-lactam and glycopeptide resistance in S. aureus.
Copyright (C) 2003 Blackwell Publishing Ltd.