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 requires the understanding of local transmission pathways to target effective disease control interventions. In this study, we characterised the genomic diversity of M. bovis across Wales by ana-lysing 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 most other Welsh isolates, suggesting independent intro-ductions 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, SNPs were identified in coding genes that have the potential for important advantageous physiological consequences that may impact host-pathogen interactions and necessitate further investigation.