title: Distinct mechanisms of DNA repair in mycobacteria and their implications in attenuation of the pathogen growth.
abstract: About a third of the human population is estimated to be infected with Mycobacterium tuberculosis. Emergence of drug resistant strains and the protracted treatment strategies have compelled the scientific community to identify newer drug targets, and to develop newer vaccines. In the host macrophages, the bacterium survives within an environment rich in reactive nitrogen and oxygen species capable of damaging its genome. Therefore, for its successful persistence in the host, the pathogen must need robust DNA repair mechanisms. Analysis of M. tuberculosis genome sequence revealed that it lacks mismatch repair pathway suggesting a greater role for other DNA repair pathways such as the nucleotide excision repair, and base excision repair pathways. In this article, we summarize the outcome of research involving these two repair pathways in mycobacteria focusing primarily on our own efforts. Our findings, using Mycobacterium smegmatis model, suggest that deficiency of various DNA repair functions in single or in combinations severely compromises their DNA repair capacity and attenuates their growth under conditions typically encountered in macrophages.
authors: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.
authors: Krishna
authors: K
authors: Kurthkoti
authors: Umesh
authors: U
authors: Varshney
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015687:Cell Hypoxia; D004249:DNA Damage; D004260:DNA Repair; D024881:Drug Resistance, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005838:Genotype; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D050296:Microbial Viability; D009154:Mutation; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity; D010641:Phenotype; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species