Investigating the genomic basis of antimicrobial resistance in Mycobacterium tuberculosis (Mtb) using genome-wide methodologies

Data Strategic Research Priority: World Class Biosciences
Strategic Research priority: Bioscience for Health
Abstract
Tuberculosis, caused by different lineages M. tuberculosis strains, is an important global public health issue. Drug resistance is a serious challenge to effective control, while Mtb sequencing can provide insights into resistance mutations and classify strain-types that have differential roles in pathogenesis and disease outcome.

Project
Using a global dataset of whole genome sequenced Mtb isolates (n > 18,000), we will investigate the effect of lineage-specific variation, using genome-wide association, machine learning and phylogenetic approaches to:
(1) elucidate antimicrobial resistance in M. tuberculosis;
(2) describe the shared genomics of highly resistant, and potentially transmissible M. tuberculosis isolates.
(3) identify genetic interactions within the M. tuberculosis genome in relation to antimicrobial resistance phenotypes.

With each analysis approach uncovering potentially different mechanisms of association, this work will uncover fundamental insights into the process of drug resistance and transmission of these phenotypes.