Mechanism of Reduced Vancomycin Susceptibility Conferred by walK Mutation in Community-Acquired Methicillin-Resistant Staphylococcus aureus Strain MW2
Mechanism of Reduced Vancomycin Susceptibility Conferred by walK Mutation in Community-Acquired Methicillin-Resistant Staphylococcus aureus Strain MW2
复制标题
社区获得性耐甲氧西林金黄色葡萄球菌MW2株中walk突变导致万古霉素敏感性降低的机制
DOI：
10.1128/aac.04290-14
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发表时间：
2015-02-01
影响因子：
4.9
通讯作者：
Sun, Baolin
中科院分区：
文献类型：
--
作者：
Hu, Jinfeng;Zhang, Xu;Sun, Baolin
分子机制不明确的点突变常与金黄色葡萄球菌万古霉素耐药有关。在这里，我们观察到walK （G223D）突变导致细胞壁代谢相关基因表达减少，自溶活性降低，细胞壁增厚，万古霉素敏感性降低。磷酸化分析显示WalK （G223D）表现出减少的自磷酸化，这导致了WalR磷酸化的减少。电泳迁移率转移试验表明，WalK （G223D）磷酸化的WalR与atlA启动子结合的能力降低。
ABSTRACT Point mutations with unclear molecular mechanisms are often associated with vancomycin resistance in Staphylococcus aureus. Here, we observed that the walK (G223D) mutation caused decreased expression of genes associated with cell wall metabolism, decreased autolytic activity, thickened cell walls, and reduced vancomycin susceptibility. A phosphorylation assay showed that WalK (G223D) exhibited reduced autophosphorylation, which led to reduced phosphorylation of WalR. An electrophoretic mobility shift assay indicated that WalK (G223D)-phosphorylated WalR had a reduced capacity to bind to the atlA promoter.