Hu Jinfeng, Zhang Xu, Liu Xiaoyu, Chen Chuan, Sun Baolin
Department of Microbiology and Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui, China.
Department of Microbiology and Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui, China Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China
Antimicrob Agents Chemother. 2015 Feb;59(2):1352-5. doi: 10.1128/AAC.04290-14. Epub 2014 Dec 1.
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.
分子机制不明的点突变通常与金黄色葡萄球菌对万古霉素的耐药性有关。在此，我们观察到walK（G223D）突变导致与细胞壁代谢相关的基因表达降低、自溶活性降低、细胞壁增厚以及对万古霉素的敏感性降低。磷酸化分析表明，WalK（G223D）的自磷酸化减少，这导致WalR的磷酸化减少。电泳迁移率变动分析表明，WalK（G223D）磷酸化的WalR与atlA启动子结合的能力降低。
