Discovery and validation of pathogen specific biomarkers and comparative genomics for diagnosis and tracking of bovine tuberculosis

Abstract

Current tools for the detection of Mycobacterium tuberculosis complex infections notably M. bovis are inadequate. New methods are required that are quick, inexpensive and accurate. In addition, the contribution of Mycobacterium bovis to the proportion of tuberculosis cases in humans is unknown. In this thesis, these questions were addressed by applying novel minimally invasive tools-pathogen specific peptides and circulating small and miRNA (biomarkers) - to detect infection with Mycobacterium tuberculosis complex organisms quickly, efficiently and accurately. Whole genome sequencing was also carried out and used to extract a minimum Single Nucleotide Polymorphism (SNP) set that would be used in a SNP chip as a means to quickly detect Mycobacterium tuberculosis complex infection. Genome analysis in this study identified M. bovis in humans and great apes suggesting transmission from domesticated ruminants is possible in high TB prevalence regions of the world due to a dynamic and changing interface, which has created opportunity for exposure and transmission. These tools all offer specific approaches for the early identification of M. bovis and other Mycobacterium tuberculosis complex infections.