Uncovering the Genomic Landscape of Mycobacterium bovis in Wales

Bovine tuberculosis (bTB), caused by the bacterium Mycobacterium bovis, is one of the most pressing animal health issues in Wales today. It negatively impacts cattle health, affects profitability and trade, and can decimate years of genetic improvement towards desirable production traits. It also places a significant burden on the health and well-being of affected farming families. Eradication of bTB re-quires the understanding of local transmission pathways to target effective disease control interventions. Traditional genotyping methods, such as spoligotyping and VNTR analysis, which have previously been used in Wales to understand the epidemiology of M. bovis, have lacked the discriminatory power to accurately identify local transmission pathways. Recently, whole-genome sequencing has replaced traditional genotyping methods for all M. bovis strains isolated from infected animals in Wales. In this study, we characterised the genomic diversity of M. bovis across Wales by analysing the genome sequence of all 379 M. bovis isolates obtained from culture-positive animals in Wales in 2021. Analyses uncovered three main clusters that are geographically distinct. A further three clusters containing fewer isolates were also geographically separated, two of which had particularly large SNP distances compared to the majority of other Welsh isolates, suggesting independent introductions of M. bovis strains that are not endemic to Wales. Fine-scale and epidemiologically relevant genetic structuring was identified within the six main clusters, indicating region-specific evolution, which can drive local disease dynamics. Finally, A number of SNPs in coding genes were identified that have the potential for important advantageous physiological consequences that may impact host-pathogen interactions and necessitate further investigation.