动物相关MRSA的种属特异性分子标志物及跨种属传人风险预测

The “super bacteria” of methicillin-resistant staphylococcus aureus (MRSA) has become the most important multidrug-resistant bacteria in hospital and community infections. It is noteworthy that recently new type of livestock-associated MRSA (LA-MRSA) was discovered, and invaded into the communities and hospitals and caused great threat to the human health and life. In china, the study of LA-MRSA was limited to monitoring studies of animal specimens. Previous research in our study group reveals that LA-MRSA may spread across species causing human infection. Previous studies of LA-MRSA mainly limited to the surveillance of animal samples, and the genetic evidence of cross-species transmission is limit and the risk of cross-species transmission is still not known. This study intends to comprehensively test the variable genes in the core genome and the mobile genetic elements in the accessory genome and its encoding genes of animal and human MRSA strains. The dimensionality reduction method and discriminant analysis were used to reveal the species-specific molecular markers of animal and human MRSA, and to predict the risk of cross-species transmission of LA-MRSA from animals to the population. This study provides the genetic evidence for the MRSA tracing, and also provides genetic markers for medicine practice, such as the early screening of the MRSA among high risk animal-related practitioners and targeted drug development.

“超级细菌”耐甲氧西林金黄色葡萄球菌（MRSA）已成为医院和社区感染的最重要多重耐药菌。值得关注的是，近年来发现新型的动物相关MRSA（LA-MRSA）侵入到社区和医院中，对人类健康和生命造成极大的威胁。课题组前期流行病学研究已提示LA-MRSA可能通过动物途径跨种属导致人感染。既往LA-MRSA研究主要局限于动物标本的监测研究，因此尚缺乏LA-MRSA跨种属传人的遗传证据，且跨种属传人的风险也尚未清楚。本研究全面检测动物源与人源MRSA核心基因组的可变基因、附属基因组的可移动遗传元件及其编码的相关基因，系统阐明动物源与人源MRSA的遗传背景；利用降维和判别分析策略揭示动物源与人源MRSA种属特异性分子标志物，并预测LA-MRSA跨越动物种属传播给人群的风险。本研究为MRSA的追踪溯源提供遗传学证据,也为高危动物从业人员MRSA的早期筛查和靶向性药物开发等医学实践提供遗传学标志物。

“超级细菌”耐甲氧西林金黄色葡萄球菌（MRSA）已成为医院和社区感染的最重要多重耐药菌。在我国，动物相关MRSA (LA-MRSA)的流行病学研究尚未大规模开展。前期研究揭示LA-MRSA可能跨越种属引起人感染，但LA-MRSA跨种属传人的遗传证据和传播风险仍然不明。.. 本研究系统阐明动物源与人源MRSA的遗传背景，并揭示动物源与人源MRSA的种属特异性分子标志物（包括CC9、scn基因、四环素耐药等），为MRSA的追踪溯源提供遗传学证据，也为高危人群MRSA的早期筛查以及靶向性药物研发等医学实践提供遗传标志物。.. 基于动物源与人源MRSA的遗传背景，利用距离判别、logistic判别函数建立预测菌株来源的二分类判别模型；距离判别、logistic判别函数预测动物从业人员携带动物源MRSA比例分别为52.3%和50.8%，揭示LA-MRSA跨种属传播机制，对制定有效措施预防和控制LA-MRSA在人群中传播具有重要的指导意义。.. 依托本项目，课题负责人在权威医学期刊发表论文15篇，包括高质量SCI收录12篇(其中通讯作者发表SCI论文11篇)和中文核心论文3篇，超额完成项目申请书中预期成果（即预期在权威医学杂志上发表2-4篇高质量论文）。