Nachappa, Somanna Ajjamada and Neelambike, Sumana M. and Ramachandra, N. B. (2022) Differential expression of the Mycobacterium tuberculosis heat shock protein genes in response to drug-induced stress. Tuberculosis, 134. ISSN 1472-9792
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Heat shock proteins are essential in maintaining cellular protein function, especially during stress. Their influence in managing drug-induced stress in Tuberculosis is not clearly understood. Aims: Study the expression of select genes of the DnaK/ClpB chaperone network to evaluate their role in stress response in Mycobacterium tuberculosis clinical isolates during exposure to Isoniazid (INH) and Rifampicin (RIF). Methods: Sanger sequencing to detect drug-resistant mutations followed by Drug Susceptibility Testing and Minimum Inhibitory Concentration determination. Culturing the bacilli in vitro, exposed to 1/4, 1/2 and 1 x MIC, and RNA quantification of dnaK, dnaJ1, grpE and clpB genes by using Real-time PCR. Results: Susceptible isolates showed marginal down-regulation of two genes for INH, whereas all genes underexpressed against RIF. INH-resistant isolates had distinct expression profiles for inhA-15 and katG315 mutants. RIF-resistant bacilli did not have significant differential expression. MDR isolate showed up-regulation of all the four genes, with two genes over-expressing (>= 4-fold). Conclusions: We observed characteristic gene expression profiles for each isolate in response to lethal and sublethal doses of INH and RIF. This provides insight into the role of DnaK/ClpB chaperone network in managing drug-induced stress and facilitating resistance. Further, the knowledge could provide targets for new drugs and augmenters.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Tuberculosis; Heat shock protein; Drug resistance; Gene expression |
| Subjects: | B Life Science > Genetics and Genomics |
| Divisions: | Department of > Genetics and Genomics |
| Depositing User: | C Swapna Library Assistant |
| Date Deposited: | 04 Sep 2023 10:25 |
| Last Modified: | 04 Sep 2023 10:25 |
| URI: | http://eprints.uni-mysore.ac.in/id/eprint/17720 |
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