Partnership to investigate the emergence of MRSA clones in cattle and their transmission to man.

This research results from the recent discovery of methicillin-resistant Staphylococcus aureus (MRSA) in dairy cattle in the UK that possess a divergent gene responsible for antibiotic resistance combined with the detection of the same divergent gene in a hospital MRSA isolate. This project is designed to answer questions about the prevalence of MRSA possessing the divergent gene in people, and in dairy cattle, and also to see if people closely associated with dairy farms are more likely to harbour the new MRSA. The research will take advantage of the latest genome sequencing technology through a partnership between the Wellcome Trust Sanger Institute, the University of Cambridge and the Moredun Institute. The research itself will involve a survey of MRSA isolates obtained from 6 regional hospitals, a survey of 600 dairy herds and a case-control-study comparing herds infected with the novel MRSA and unaffected herds. The case-control study will also provide an opportunity to look at other staphylococcal species (coagulase negative staphylococci) that cause mastitis in dairy cows, and are known to have high levels of methicillin resistance, for evidence of the origins of the methicillin resistance gene. Genome sequencing will be used both to search the bacterial genomes for genetic mechanisms that are responsible for conferring antibiotic resistance and to look at family trees in fine detail to provide evidence of transmission and micro-evolution of MRSA.

MRSA is a major public health problem, which is exacerbated by emergence of new MRSA strains in community settings and animal populations. For example, MRSA ST398 emerged from the pig population in mainland Europe and is now widespread in man. The discovery of a novel bovine associated SCCmec, carrying a divergent mecA gene, from a phenotypically MRSA strain on a dairy farm, and its subsequent isolation from a human clinical sample, highlights the importance, to human health, of animal MRSA as a potential reservoir of emerging MRSA strains. Through a partnership grant, relevant medical and veterinary expertise will be combined to address the importance of this novel MRSA for human medicine. The proposed partnership between the Department of Veterinary Medicine and the Department of Medicine/HPA at Cambridge, the Moredun Research Institute, and the Wellcome Trust Sanger Institute will provide a unique combination of expertise in the fields of MRSA research, farm animal infectious disease research, and cutting edge bacterial genomics research to investigate emerging methicillin resistant veterinary isolates. The planned work will establish their prevalence in human and animal populations, and examine the potential for interspecies transmission. A survey of MRSA acquired from hospital screening, collecting 2100 isolates from 6 regional hospitals, will collate all MRSA that are not caused by carriage of conventional mecA. A parallel farm level prevalence survey of 600 dairy herds will be performed using bulk milk samples. Subsequently a farm level case control study will be performed to determine if there is an association between people, who work or live on farms where divergent mecA MRSA are present, and carriage of divergent mecA MRSA. Coagulase negative staphylococci, which are common bovine mastitis pathogens and a potential source of mecA, will be subjected to genome sequencing on case farms to look at mecA diversity and for evidence of possible transmission of SCCmec. Genome sequencing will also be used to perform a SNP analysis of groups of isolates, that share a sequence type and cross the host species divide, to provide a fine resolution phylogenetic analysis. The phylogenetic analysis will help us understand the micro-evolution and transmission of these novel MRSA. The research to be undertaken by the partnership will help us measure and understand the risks to human health; they will also provide a valuable insight into the origins and mechanisms of antibiotic resistance in farm animal associated MRSA.