title: Two-component system VraSR positively modulates the regulation of cell-wall biosynthesis pathway in Staphylococcus aureus.
abstract: 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.
authors.affiliation: Bacteriology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. mkuroda@med.juntendo.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuroda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kuroda
authors.forename: Taku
authors.initials: T
authors.lastname: Oshima
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Takeuchi
authors.forename: Hirotada
authors.initials: H
authors.lastname: Mori
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hiramatsu
mesh_terms: 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
chemical_list: 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