Antimicrobial Resistance in Mycobacterium tuberculosis: The Odd One Out

Antimicrobial resistance (AMR) threats are typically represented by bacteria capable of extensive horizontal gene transfer (HGT). One clear exception is Mycobacterium tuberculosis (Mtb). It is an obligate human pathogen with limited genetic diversity and a low mutation rate which lacks any evidence for HGT. Such features should, in principle, reduce its ability to rapidly evolve AMR. We identify key features in its biology and epidemiology that allow it to overcome its low adaptive potential. We focus in particular on its innate resistance to drugs, its unusual life cycle, including an often extensive latent phase, and its ability to shelter from exposure to antimicrobial drugs within cavities it induces in the lungs.

TrendsThe clonal reproduction mode and low mutation rate of Mycobacterium tuberculosis (Mtb) makes the bacterium an a priori unlikely resistance threat. Despite this, drug-resistant tuberculosis (TB) has become a major public health threat, leading to massive costs in human and economic terms.In addition to the recent emergence of antimicrobial resistance, mycobacteria are unusually challenging to treat clinically due to ancestral intrinsic antibiotic resistance.Mtb can create pulmonary cavities that are hidden from immune factors and only poorly accessible to antimicrobial drugs, yet harboring large populations of bacteria, thus offering the perfect conditions for the development of resistance.Highly transmissible multiresistant Mtb strains have emerged following the use of the same antimicrobial compounds for over four decades.