Abstract | BACKGROUND: Targeting persistent tubercule bacilli has become an important challenge in the development of anti-tuberculous drugs. As the glyoxylate bypass is essential for persistent bacilli, interference with it holds the potential for designing new antibacterial drugs. We have developed kinetic models of the tricarboxylic acid cycle and glyoxylate bypass in Escherichia coli and Mycobacterium tuberculosis, and studied the effects of inhibition of various enzymes in the M. tuberculosis model. RESULTS: CONCLUSION: We used kinetic modeling of biochemical pathways to assess various potential anti-tuberculous drug targets that interfere with the glyoxylate bypass flux, and indicated the type of inhibition needed to eliminate the pathogen. The advantage of such an approach to the assessment of drug targets is that it facilitates the study of systemic effect(s) of the modulation of the target enzyme(s) in the cellular environment.
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Authors | Vivek Kumar Singh, Indira Ghosh |
Journal | Theoretical biology & medical modelling
(Theor Biol Med Model)
Vol. 3
Pg. 27
(Aug 03 2006)
ISSN: 1742-4682 [Electronic] England |
PMID | 16887020
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antitubercular Agents
- Glyoxylates
- glyoxylic acid
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Topics |
- Antitubercular Agents
(pharmacology)
- Citric Acid Cycle
(drug effects, physiology)
- Gene Deletion
- Gene Expression Regulation, Bacterial
- Glyoxylates
(metabolism)
- Kinetics
- Models, Biological
- Mycobacterium tuberculosis
(drug effects, genetics, metabolism)
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