Phylogenetic analysis of Mycobacterium caprae highlights past and present epidemiological links at the Iberian Peninsula scale

Mycobacterium caprae is linked to regular outbreaks of tuberculosis (TB) in geographically distinct caprine populations across Europe, namely Iberia where this ecovar may represent up to 8% of total animal TB cases, circulating in multi-host communities encompassing domestic ruminants and wildlife, representing severe financial losses. It also causes zoonotic human disease. In this work, we undertake the first phylodynamic and phylogeographic analyses of M. caprae to reconstruct past demography and transmission chains. First, we examined the worldwide diversity of M. caprae based on 229 unpublished and publicly available whole genome sequences, depicting Asian, Central-East European, and Iberian clades. Phylodynamic analyses of the SB0157 Iberian clade (n 1/4 81) positioned the most recent common ancestor in goats, around 100 years ago. Host transition events were common between goats, wild boars, and humans, possibly resulting from mixed farming, extensive management, and close human proximity, facilitating interspecific transmission. We show the spread of M. caprae on multiple scales due to local and transnational animal trade, supporting historical and sustained cross-species transmission in Iberia. We highlight the value of intersecting genomic epidemiology with molecular ecology to resolve epidemiological links and show that an EU-official eradication program in goats is utterly needed to control TB in a multi-host scenario.