When Two Genomes Go to War—New Perspectives for Bovine TB Research and Control

Advances in pathogen genomics have enabled exploration of the evolution and diversity of the Mycobacterium tuberculosis complex (MTBC) at unprecedented resolution. These bacilli were thought to be genetically homogeneous with limited phenotypic diversity. However, pathogen genomics provides a more nuanced picture, revealing significant genotypic and phenotypic diversity. For example, the human-adapted pathogen, M. tuberculosis exhibits heterogeneity in epidemiologically relevant traits, such as virulence and transmissibility. Less is known about how genetic heterogeneity in M. bovis may affect disease outcomes and epidemiology in livestock. Concurrently, the genetic architecture influencing host response to exposure and infection with the MTBC in humans and animals has been investigated, revealing that host susceptibility is moderately heritable and polygenic. In cattle, this knowledge has been exploited to develop breeding indices for genetic selection to cumulatively reduce susceptibility of cattle populations to bovine TB (bTB). Additionally, exploitable genetic variation in host bTB infectivity has been demonstrated. There is, therefore, evidence on how pathogen and host genetic variation, in isolation, can affect bTB epidemiological processes. However, disease outcome is largely determined by how pathogens and hosts interact, in particular the interplay between pathogen virulence and host susceptibility and pathogen transmissibility and host infectivity. Understanding of the genetic basis of these interactions is, however, limited. bTB is a persistent and costly problem in the UK and Ireland, with eradication proving elusive. Filling existing knowledge gaps in host and pathogen genetics research and uniting these genetic data sources is timely and may translate to exploitable outcomes which enhance eradication efforts. Here, we provide an overview of current insights and knowledge gaps in how host and pathogen genetic diversity can affect disease outcomes following exposure to TB bacteria. We explore tentative work at the host-pathogen genetic interface and describe a research strategy that could provide relevant novel insights into bTB epidemiology.