Drug resistance is best thought of as an ongoing biological process. Resistant bacteria must emerge, become established and ultimately transmit in order to be relevant to human health. In this context, genetic diversity can influence the rate and likelihood of resistance emerging; it can also modulate the net physiological impact of resistance and the propensity of an organism to improve any defects that arise from it. Combined, these effects can have an impact on a larger scale, with highly transmissible drug-resistant bacterial strains posing a formidable threat to global health. These considerations are pertinent to the future of tuberculosis control as well. In this chapter, we review our current understanding of the impact of genetic diversity in the broadest sense on the evolution of drug-resistant members of the Mycobacterium tuberculosis complex.
Keywords: Drug resistance; Epistasis; Evolution; Fitness Landscape.