title: Drug-susceptible Mycobacterium tuberculosis Beijing genotype does not develop mutation-conferred resistance to rifampin at an elevated rate.
abstract: 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.
authors.affiliation: Department of Bacteriology, Swedish Institute for Infectious Disease Control, Solna, Sweden. jim.werngren@smi.ki.se
authors.forename: Jim
authors.initials: J
authors.lastname: Werngren
authors.forename: Sven E
authors.initials: SE
authors.lastname: Hoffner
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D003470:Culture Media; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D012293:Rifampin / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D003470:Culture Media; D012293:Rifampin