金黄色葡萄球菌万古霉素中度耐药机制的研究

金黄色葡萄球菌（金葡菌）是人类的主要致病菌，可导致严重的临床感染。近年来，世界范围内MRSA、VISA与VRSA的不断出现和传播已成为金葡菌治疗的重大难题。其中金葡菌万古霉素中度耐药（VISA）发生的原因主要是基因突变，但其分子机制的阐释尚未完善。已经报道的与VISA发生相关的基因主要有vraSR，graSR，rpoB和walK,然而这些基因突变并不出现在所有VISA中，说明其它基因位点及其相关分子机制能够导致万古霉素敏感性下降。我们在前期工作中发现,实验室万古霉素压力诱导的VISA中存在三个基因的点突变，分别为walk, ftsz和rpoc,其中ftsz和rpoc与VISA发生的相关性目前尚无报道。本项目拟深入研究ftsz和rpoc对该VISA菌株万古霉素敏感性的影响，并阐释相关的分子机制。该研究将加强对金葡菌耐药机制的认识，进而为金葡菌的临床治疗和检测提供新的理论基础和治疗策略。

Staphylococcus aureus is an important human pathogen that often causes serious clinical infections. In recent years, worldwide emergence and spread of MRSA, VISA, and VRSA strains have posed big challenges to clinical treatment of S. aureus infecton. The reason underlying drug resistance is mainly due to gene mutation, but the interpretation of the molecular mechanism has not been elucidated yet. Recent studies have pointed out that a number of mutations that link drug resistance were found in some VISA strains, such as vraSR, graSR, rpoB, and walK. However, except for the mutations in vraSR and graRS, the role of the mutations found in VISA has not been established. We have obtained a VISA strain by giving vancomycin stress, and genome sequencing indicates that our VISA strain harbors point mutations in three genes, walk, ftsz, and rpoc, respectively. No previous report has linked ftsz and rpoc to VISA. In this proposal, we aim to investigate the influence of ftsz and rpoc on vancomycin susceptibility and elucidate the molecular mechanisms underlying the resistance. This study should not only add the knowledge of the molecular mechanisms of drug resistance, but also provide the new strategy for the clinical treatment of S. aureus infection.