Abstract
Tuberculosis, caused by Mycobacterium tuberculosis (Mtb) is an ancient disease that has remained a leading cause of infectious death. Mtb has evolved drug resistance to every antibiotic regimen ever introduced, greatly complicating treatment, lowering rates of cure and menacing TB control in parts of the world. As technology has advanced, our understanding of antimicrobial resistance has improved, and our models of the phenomenon have evolved. In this review, we focus on recent research progress that supports an updated model for the evolution of drug resistance in Mtb. We highlight the contribution of drug tolerance on the path to resistance, and the influence of heterogeneity on tolerance. Resistance is likely to remain an issue for as long as drugs are needed to treat TB. However, with technology driving new insights and careful management of newly developed resources, antimicrobial resistance need not continue to threaten global progress against TB, as it has done for decades.