表面蛋白Ebh在甲氧西林耐药金黄色葡萄球菌致病力中的作用研究

甲氧西林耐药金黄色葡萄球菌（MRSA）致死率高，已成为血流感染、心内膜炎等医院感染的重要致病菌。甘肃省细菌耐药监测数据表明，该菌已跃居各类感染的第二位。Ebh是其重要的表面蛋白，易于被药物分子或抗体接触。我们前期对本地区流行菌株进行分子流行病学调查，MRSA中ebh基因携带率达45.8%。且初步证实，ebh基因阳性菌株易产生生物膜，在人血浆中的凝集力随着时间的延长而增加，但其在MRSA克隆流行中的作用尚不明确。我们推测Ebh蛋白在本地区流行株MRSA-ST239细胞粘附、细菌聚集、生物膜形成及对小鼠毒力等致病力中发挥主要作用，可能是导致本地区菌株播散的重要原因之一，具体致病作用有待进一步探究。本项目拟通过菌株构建、动物模型构建、皮肤上皮细胞粘附实验等一系列实验，探明Ebh在MRSA-ST239致病力中发挥的作用，为开发针对本地区流行株关键致病因子的药物或疫苗提供潜在靶标。

The infection of methicillin-resistant staphylococcus aureus (MRSA) leads to a high fatality rate. MRSA has become a crucial pathogenic bacterium for infections such as bloodstream infection and endocarditis in the hospital. According to the monitoring data of bacterial resistance in Gansu province, MRSA has already become the second most infectious bacteria , and Ebh ,which can be easily contacted by pharmaceutical molecules or antibodies, is an important surface protein for MRSA. From the early molecular epidemiological investigation for the epidemic strains in this region, we have found that in MRSA the ebh gene carrying rate was 45.8%. And it has been preliminarily confirmed that the positive strains in Ebh can product biofilms easily, and the cohesion in human plasma is increasing over time, however, the function of these positive strains is still not clear, especially for the role it plays in MRSA cloning prevalence. We hypothesize that for the various pathogenicity of MRSA-ST239 in this region, the Ebh protein is playing a dominating role in the local epidemic strains, in terms of cell adhesion, bacterial aggregation, biofilm formation and the virulence of mice, and it may be one of the most crucial factors for the dissemination of the epidemic strains in this region. However, the accurate pathogenic factor still needs a further investigation. This project intends to find the role of Ebh plays for the pathogenicity of MRSA-ST239, through a strain construction, an animal modeling, and a skin epithelial cell adhesion test etc., and it intends to provide a potential target for the medicine or vaccine aming for the key pathogenic factors of the epidemic strains in this region.