Tuberculosis drug resistance

The evolution of compensatory mutations in drug resistant Mycobacterium tuberculosis strains is reported this week in Nature Genetics. This suggests an important role for compensatory mutations in the evolution and spread of drug resistant tuberculosis (TB) in current global epidemics. Sebastien Gagneux and colleagues report the whole-genome sequencing of clinical M. tuberculosis strains isolated from ten individuals with TB, including both rifampicin drug resistant and rifampicin sensitive strains isolated from each individual. The authors also sequenced experimentally evolved M. tuberculosis strains that developed rifampicin-resistance. These laboratory-evolved resistant strains all contained rpoB mutations known to confer rifampicin resistance. They identified the evolution of compensatory mutations in the rpoA and rpoC genes associated with increased fitness, found both in the laboratory evolution studies and at high frequencies in world-wide clinical settings and amongst epidemics of multiple-drug resistant (MDR)-TB.