Mutations in mutT genes of Mycobacterium tuberculosis isolates of Beijing genotype.

Missense alterations in genes mutT4 and mutT2, which encode DNA repair enzymes, were sequenced from 30 clinical isolates of Mycobacterium tuberculosis of Beijing genotype, mostly from patients with primary tuberculosis, to evaluate their contribution to anti-mycobacterial drug resistance. The mutation Arg to Gly at codon position 48 (CGG to GGG) of mutT4 was found in 21 isolates; of these, 16 isolates also harboured the mutation Gly to Arg at position 58 (GGA to CGA) of mutT2. No statistically significant association was found between mutT4 and mutT2 mutations, and drug resistance. Furthermore, no mutations in mutT4 or mutT2 were found in any of 24 isolates resistant to multiple drugs, nor in 28 anti-mycobacterial drug-susceptible isolates of different genotypes. These data confirm that the polymorphism of mutT genes is characteristic and unique to the Beijing phylogenetic lineage. The mutator phenotype does not appear to increase prevalence of drug resistance, but further studies are required to investigate the mutation rates of Beijing isolates in response to drug exposure.