Two-component system VraSR positively modulates the regulation of cell-wall biosynthesis pathway in Staphylococcus aureus.
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.
Kuroda
Makoto
M
Bacteriology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. mkuroda@med.juntendo.ac.jp
Kuroda
Hiroko
H
Oshima
Taku
T
Takeuchi
Fumihiko
F
Mori
Hirotada
H
Hiramatsu
Keiichi
K
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001414:Bacitracin / Q000494:pharmacology; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D015296:Ceftizoxime / Q000494:pharmacology; D002473:Cell Wall / Q000378:metabolism*; D004268:DNA-Binding Proteins; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005578:Fosfomycin / Q000494:pharmacology; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D015378:Imipenem / Q000494:pharmacology; D016106:Methicillin Resistance / Q000235:genetics; D008826:Microbial Sensitivity Tests; D020411:Oligonucleotide Array Sequence Analysis; D010068:Oxacillin / Q000494:pharmacology; D012329:RNA, Bacterial / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017334:Teicoplanin / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014640:Vancomycin / Q000494:pharmacology*; D018440:beta-Lactam Resistance / Q000235:genetics
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C478170:VraR protein, Staphylococcus aureus; C478169:VraS protein, Staphylococcus aureus; D001414:Bacitracin; D005578:Fosfomycin; D017334:Teicoplanin; D014640:Vancomycin; D015378:Imipenem; D015296:Ceftizoxime; D010068:Oxacillin