DNA metabolism in Mycobacterium tuberculosis: Implications for drug resistance and strain variability

In this paper, we review the evidence supporting the notion that the genome of Mycobacterium tuberculosis sustains considerable damage as a result of exposure to nitrosative and oxidative stress. On these grounds, we propose a model in which stress-induced DNA damage in M. tuberculosis plays a role in the evolution of chromosomally encoded drug resistance mutations by alte ring the global mutation rate by mechanisms akin to SOS mutagenesis. Finall y we review some of the factors determining the evolution of PE/PPE and MIR U (There are many abbreviations in this paper which are not defined, e.g. S OS, PE/PPE and MIRU. Please indicate whether these are well known and will be understood by readers or whether they should be defined at first mention ) loci whose sequence characteristics are suggestive of their classificatio n as heritable local mutators.