Identification of factors that led to the development of pig-associated epidemic MRSA clone

导致猪相关流行性 MRSA 克隆发展的因素的鉴定

• 批准号: 389553136
• 负责人: Professor Dr. Stefan P. Schwarz
• 金额: --
• 依托单位: National Natural Science Foundation of China
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/389553136?language=en
• 关键词: Identification; factors; led; development; pig

Since the mid-2000s, livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) isolates have been identified among pigs in Germany, China and in various other parts of the world. In pigs, LA-MRSA isolates usually occur as colonizers; diseases caused by them are rarely seen. Molecular analysis of the LA-MRSA isolates by multi-locus sequence typing identified the dominant clones of LA-MRSA in China to belong to the clonal complex (CC) 9, whereas the dominant LA-MRSA clones in the rest of the world were assigned to CC398. The reason for this difference is unknown. The aim of the proposed project is to find out the factors that led to the development of a pig-associated epidemic MRSA clone. For this, we propose a collaborative approach including a comprehensive and comparative analysis of (i) the epidemiologically successful colonizing LA-MRSA CC9 from China and their non-successful counterparts from Germany but also (ii) the epidemiologically successful colonizing LA-MRSA CC398 from Germany and their non-successful counterparts from China. Whole genome sequencing and detailed analysis of the core genome and the accessory genome will provide details about the genetic composition of the successful versus non-successful colonizers belonging to the same CC. Genes present in the successfully colonizing isolates but absent in the non-successfully colonizing isolates will be analysed for their role in virulence, adherence, survival or regulatory processes. Moreover, all four groups of isolates will be investigated for their metabolic properties, fitness, survival rates, adhesion to epithelial cells, capacity of biofilm formation, and growth characteristics. In particular, we want to determine whether (or not) the successful colonizers outcompete the non-successful colonizers under in-vitro and in-vivo conditions and how colonization with a successful colonizer changes the nasal microbiome. Transcriptome studies will reveal the genes of different LA-MRSA CC9 and CC398 isolates that are up- and down-regulated after having colonized the porcine anterior nares. Finally, the transferability of SCCmec cassettes from LA-MRSA CC398 and CC9 clones into methicillin-susceptible S. aureus (MSSA) will be investigated to gain insight into the rise of new MRSA clones. The anticipated results will provide important basic information regarding the factors that led to the development of epidemic MRSA clones. This will help to design prevention and intervention measures to keep pigs (and possibly also other food-producing animals) free of LA-MRSA.

自2000年代中期以来，在德国、中国和世界其他地区的猪中已经鉴定出家畜相关的耐甲氧西林金黄色葡萄球菌(LA-MRSA)分离株。在猪中，LA-MRSA分离物通常以定殖者的形式出现，由它们引起的疾病很少见。多位点序列分析表明，中国的LA-MRSA优势克隆属于克隆复合体(CC)9，而世界其他地区的LA-MRSA优势克隆归属于CC398。造成这种差异的原因尚不清楚。拟议项目的目的是找出导致猪相关流行性MRSA克隆的因素。为此，我们提出了一种合作的方法，包括对(I)中国及其德国同行在流行病学上成功定植LA-MRSA CC9，以及(Ii)德国LA-MRSA CC398与中国未成功定植的流行病学成功定植的病例进行全面和比较分析。对核心基因组和附属基因组的全基因组测序和详细分析将提供属于同一CC的成功和不成功殖民者的遗传组成的细节。在成功定殖的菌株中存在但在未成功定植的菌株中缺失的基因将被分析其在毒力、粘附性、生存或调节过程中的作用。此外，将对所有四组分离株的代谢特性、适应性、存活率、与上皮细胞的粘附性、生物被膜形成能力和生长特性进行调查。特别是，我们想要确定在体外和体内条件下，成功的定殖者是否比不成功的定殖者竞争，以及成功的定殖者的定植如何改变鼻部微生物群。转录组研究将揭示不同LA-MRSA CC9和CC398分离株的基因在定植于猪前鼻孔后上调和下调。最后，将研究从LA-MRSA CC398和CC9克隆的SCCmec盒转移到甲氧西林敏感的金黄色葡萄球菌(MSSA)的可能性，以深入了解新的MRSA克隆的兴起。预期结果将提供有关导致流行MRSA克隆的因素的重要基本信息。这将有助于设计预防和干预措施，使猪(可能也包括其他食用动物)不受LA-MRSA的影响。