Genomic evolution and niche adaption of Mycobacterium avium subspecies paratuberculosis

Abstract

Mycobacterium avium subspecies paratuberculosis (MAP) is a highly specialised mycobacterial pathogen that has adapted to a unique niche. It is the causative agent of Johne’s disease and incurs significant economic and welfare costs to producers and livestock. Furthermore, MAP has been associated with human Crohn’s disease, making this pathogen a public health concern. To optimise control strategies against a zoonotic pathogen, a thorough understanding of its evolution, transmission patterns and specific virulence traits is essential. The underlying mechanisms that MAP utilises to survive in the gut in multiple host species is largely unknown. This thesis begins with broader investigations to identify genomic traits specific to MAP using a combined pan-genome and mapping approach. Transcription within these MAP-specific genomic traits and regions associated with niche adaptation is then assessed. Investigations then narrow down into MAP epidemiology and strain-specific characteristics to reveal insights into host specificity and vaccine persistence phenotypes. Collectively the studies within this thesis have unveiled potential mechanisms of MAP niche adaptation and investigated genomic markers of MAP isolates that persist despite vaccination. Subspecies-specific genes identified in this work may serve as valuable diagnostic or therapeutic targets and phylogenomic analysis enables new isolates to be placed into a context. Furthermore, improvements to our understanding of MAP-specific virulence mechanisms are integral to informing the development of new targeted diagnostic tests, therapeutics and management approaches.