Identification and diversity of mixed strain infections of mycobacterium avium subspecies paratuberculosis in dairy cattle from Canadian herds

Byrne, Alexander Stephen (2023) Identification and diversity of mixed strain infections of mycobacterium avium subspecies paratuberculosis in dairy cattle from Canadian herds. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Mycobacterium avium subsp. paratuberculosis (MAP) is the pathogen responsible for Johne’s Disease (JD) in ruminants, a cause of substantial economic loss in the global dairy industry. JD is a major problem in dairy animals, and concerns have been raised regarding the association of MAP with Crohn’s Disease in humans. Mixed strain infections (MSI) refer to the concurrent infection of a susceptible host with multiple strains of a single pathogenic species. Microevolution refers to within-host changes in an infecting strain which lead to genetically distinguishable progeny. Both processes influence host-pathogen dynamics and disease progression, but not much is known about their prevalence and impact on JD. In this thesis we first conducted a systematic review on how MSIs are defined in the literature, how widespread the phenomenon is among host species and how MSIs are detected. Next, we characterized MAP isolates from 67 cows using whole genome sequencing (WGS) based methods. SNP-based analysis of WGS data, when combined with animal movement data, was able to document disease transmission between herds. Finally, up to 10 MAP isolates from 14 high-shedding animals were examined using WGS to identify the prevalence of MSIs and microevolution. Two animals showed evidence of microevolution, while the remaining twelve showed evidence of both microevolution and MSIs. Our results showed a need for further investigation of MSIs within animal-based infections, that examination of short sequence repeats allows for greater discrimination between strains, and that differences in these repeats significantly alter protein structure.

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