Two-component system VraSR positively modulates the regulation of cell-wall biosynthesis pathway in Staphylococcus aureus
Two-component system VraSR positively modulates the regulation of cell-wall biosynthesis pathway in Staphylococcus aureus
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DOI：
10.1046/j.1365-2958.2003.03599.x
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发表时间：
2003-08-01
影响因子：
3.6
通讯作者：
Hiramatsu, K
中科院分区：
文献类型：
--
作者：
Kuroda, M;Kuroda, H;Hiramatsu, K
制备了覆盖金黄色葡萄球菌N315株全基因组的DNA芯片，研究其转录谱。微阵列分析显示万古霉素诱导了139个基因的转录。其中46个基因在vraSR零突变体KVR中未被诱导。VraSR系统调控的部分基因与细胞壁生物合成有关，如PBP2、SgtB和MurZ。其他细胞壁合成抑制剂也能诱导VraSR，这表明传感器激酶VraS对细胞壁结构的损伤或细胞壁生物合成的抑制有反应。此外，来自异甲氧西林和同甲氧西林耐药金黄色葡萄球菌的vraSR零突变体对替柯planin、β -内酰胺、杆菌肽和磷霉素的耐药性显著降低，但对d -环丝氨酸和左氧氟沙星的耐药性没有显著降低。该观察结果强烈提示VraSR是细胞壁肽聚糖合成的正调节因子，深度参与了金黄色葡萄球菌β -内酰胺和糖肽耐药的表达。
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 homomethicillin-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.