Two‐component system VraSR positively modulates the regulation of cell‐wall biosynthesis pathway in Staphylococcus aureus

• Published in: Molecular microbiology Vol. 49; no. 3; pp. 807 - 821
• Main Authors: Kuroda, Makoto, Kuroda, Hiroko, Oshima, Taku, Takeuchi, Fumihiko, Mori, Hirotada, Hiramatsu, Keiichi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-08-2003
• Subjects: Anti-Bacterial Agents - pharmacology; Bacitracin - pharmacology; Bacterial Proteins - biosynthesis; Bacterial Proteins - genetics; Bacterial Proteins - physiology; beta-Lactam Resistance - genetics; Ceftizoxime - pharmacology; Cell Wall - metabolism; DNA-Binding Proteins; Drug Resistance, Multiple, Bacterial - genetics; Fosfomycin - pharmacology; Gene Expression Profiling; Gene Expression Regulation, Bacterial - drug effects; Imipenem - pharmacology; Methicillin Resistance - genetics; Microbial Sensitivity Tests; Oligonucleotide Array Sequence Analysis; Oxacillin - pharmacology; Receptors, Cell Surface - drug effects; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; RNA, Bacterial - biosynthesis; RNA, Bacterial - genetics; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Staphylococcus aureus - drug effects; Staphylococcus aureus - genetics; Staphylococcus aureus - metabolism; Teicoplanin - pharmacology; Transcription, Genetic - drug effects; Vancomycin - pharmacology
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1046/j.1365-2958.2003.03599.x

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, β‐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 β‐lactam and glycopeptide resistance in S. aureus.