Rand, Lucinda;
(2004)
The role of DNA repair genes in mycobacterium tuberculosis pathogenesis.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Mycobacterium tuberculosis is an intracellular pathogen, able to survive and replicate in macrophages. Here the bacilli encounter host defences including the production of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI). This is part of the antimicrobial response, which amongst other targets can damage DNA. It is, therefore, highly important for the bacillus to maintain mechanisms with which to repair damaged DNA. Oxidatively damaged DNA bases are removed by a variety of repair mechanisms, and studies in E. coli have identified genes that function within each of these pathways. M. tuberculosis homologues have been identified from the genome sequence, and construction and characterisation of strains defective in one or more of these genes has been used to assess the requirement for DNA damage repair in M. tuberculosis. Interestingly, strains containing individual mutations in a number of repair genes were affected in their ability to cause progressive infection in mice. In parallel with the mutational studies, global gene expression in wild-type M. tuberculosis and a recA mutant strain following DNA damage has been compared using microarrays. Generally, in bacteria DNA-damage inducible genes are regulated by the repressor protein LexA; this regulation is dependent on RecA. Thus, LexA-regulated genes are not induced in recA mutant strains. It was found that in M. tuberculosis the majority of DNA-damage inducible genes remained inducible in the recA mutant strain, including most of the inducible DNA repair genes. This suggests that non-classical regulatory mechanism(s) are important for survival of M. tuberculosis following DNA damage.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The role of DNA repair genes in mycobacterium tuberculosis pathogenesis |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| Keywords: | Health and environmental sciences; Tuberculosis |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10104505 |
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