Drug-Susceptible Mycobacterium tuberculosis Beijing Genotype Does Not Develop Mutation-Conferred Resistance to Rifampin at an Elevated Rate

The Mycobacterium tuberculosis Beijing genotype has drawn attention because it is often strongly associated with multidrug-resistant tuberculosis (MDR-TB). A possible reason is that the Beijing strains may have an enhanced capacity to develop drug resistance. In this study, we used the Luria-Delbrück fluctuation test to investigate whether strains of Beijing and non-Beijing genotypes exhibit differences in the acquisition of drug resistance. The M. tuberculosis reference strain H37Rv and 12 fully drug-susceptible clinical isolates, 6 of which were of the Beijing genotype, were examined. To determine the distribution of rifampin-resistant mutants, 25 independent cultures were made for each strain. The average mutation frequencies for the non-Beijing (H37Rv included) and Beijing genotypes were estimated to be 4.4 x 10(-8) and 3.6 x 10(-8), respectively. The corresponding average mutation rates for the non-Beijing and Beijing strains were 1.3 x 10(-8) and 1.1x 10(-8) mutations per cell division, respectively. The results suggest that the association of the Beijing genotype with MDR-TB is not due to an altered ability to develop resistance.