Mutations in putative mutator genes of Mycobacterium tuberculosis strains of the W-Beijing family

Abstract

Alterations in genes involved in the repair of DNA mutations (mut genes) result in an increased mutation frequency and better adaptability of the bacterium to stressful conditions. W-Beijing genotype strains displayed unique missense alterations in three putative mut genes, including two of the mutT type (Rv3908 and mutT2) and ogt. These polymorphisms were found to be characteristic and unique to W-Beijing phylogenetic lineage. Analysis of the mut genes in 55 representative W-Beijing isolates suggests a sequential acquisition of the mutations, elucidating a plausible pathway of the molecular evolution of this clonal family. The acquisition of mut genes may explain in part the ability of the isolates of W-Beijing type to rapidly adapt to their environment.

Figure 1

Characteristic patterns of Mycobacterium tuberculosis Beijing genotype strains.

Figure 2

MutT proteins’ sequences alignment. Mycobacterium tuberculosis Rv2985(MutT1), Rv1160(MutT2), Rv0413(MutT3), and Rv3908(MutT4) were selected from the M. tuberculosis genome because of their annotation or after a BLAST analysis. These sequences were compared to Escherichia coli mutT by using alignments available from: http://www.biochem.uthscsa.edu/~barnes/mutt.html. The detected region of similarity is shown here. #, absolutely conserved residues; *, residues that are strongly conserved and that define the mutT or nudix motif.

Figure 3

Schematic representation of a plausible pathway to explain the accumulation of mutations in mut genes.