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

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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.