The Evolution of Mycobacterium tuberculosis in HIV co-infected individuals in an HIV/TB Endemic Setting

Infection with HIV increases the risk of infection with tuberculosis (TB), and co-infection leads to acceleration of both diseases. However, the biological interactions between HIV-1, Mycobacterium tuberculosis (Mtb), and the human immune system are incompletely understood. We applied comparative genomics to investigate the impact of HIV-1 co-infection on the evolution of Mtb strains circulating in Khayelitsha, Cape Town, South Africa, a peri-urban township with high rates of HIV-associated TB. Evolutionary models, Fast Unconstrained Bayesian Approximation (FUBAR) and Model of Episodic Directional Selection (MEDS), were applied to whole-genome sequence (WGS) data for 169 Mtb strains. These phylogenetically-informed models, not previously applied to Mtb, allowed evaluation of the relative nonsynonymous (dN) and synonymous (dS) substitution rates at individual codons.