Genome epidemiology of Mycobacterium bovis infection in contemporaneous, sympatric badger and cattle populations in Northern Ireland

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Introduction Bovine tuberculosis (bTB) is an epidemiologically complex disease affecting both cattle and badgers in the UK and Ireland. Traditional molecular typing schemes have been used to characterise the spatial structure of the pathogen and relationship of M. bovis derived from sympatric animals. However, these methods lack the resolution to describe transmission dynamics at the farm level or to inform on the extent to which the hosts contribute. Whole genome sequencing can improve resolution of molecular epidemiology investigations in this epi-system. Methods We collected 598 M. bovis isolates from contemporaneous badgers (n=119) and cattle (n =479), located in a 100 km2 area of Northern Ireland. Cultures were DNA extracted and genome sequenced. Bioinformatic analysis was undertaken using the reddog pipeline and maximum likelihood phylogenetic analyses were conducted using RAxML, with the major endemic clade in the region subjected to phylodynamic analysis using Bayesian Evolutionary Analysis Sampling Trees (BEAST) software. Results and Discussion All 598 isolates produced reads of good quality, aligning to >90 % of the M. bovis reference genome with coverage of at least x10. A total of 1598 SNPs were detected. Phylogenetic analysis indicated the presence of nine major lineages circulating in the region. Eight exhibited long branch-lengths suggesting they were not endemic in the area. One lineage was endemic, comprising isolates from 60 badgers and 363 cattle. From the substitution rate of 0.36 SNPs per annum, this lineage arose in the study area in the mid-1980s. Data were consistent with ongoing transmission within and between both hosts.