Have compensatory mutations facilitated the current epidemic of multidrug-resistant tuberculosis?

Compensatory mutations have been suggested to promote multidrug-resistant tuberculosis (MDR-TB) transmission, but their role in facilitating the recent transmission of MDR-TB is unclear. To investigate the epidemiological significance of compensatory mutations, we analyzed a four-year population-based collection of MDR-TB strains from Shanghai (the most populous city in China) and 1346 published global MDR-TB strains. We report that MDR-TB strains with compensatory mutations in the rpoA, rpoB, or rpoC genes were neither more frequently clustered nor found in larger clusters than those without compensatory mutations. Our results suggest that compensatory mutations are not a major contributor to the current epidemic of MDR-TB.