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Kinetic modeling of tricarboxylic acid cycle and glyoxylate bypass in Mycobacterium tuberculosis, and its application to assessment of drug targets by Vivek Kumar Singh; Indira Ghosh is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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## 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 We used __E. coli__ to validate the pathway-modeling protocol and showed that changes in metabolic flux can be estimated from gene expression data. The __M. tuberculosis__ model reproduced the observation that deletion of one of the two __iso__citrate lyase genes has little effect on bacterial growth in macrophages, but deletion of both genes leads to the elimination of the bacilli from the lungs. It also substantiated the inhibition of __iso__citrate lyases by 3-nitropropionate. On the basis of our simulation studies, we propose that: (i) fractional inactivation of both __iso__citrate dehydrogenase 1 and __iso__citrate dehydrogenase 2 is required for a flux through t

Who reads Kinetic modeling of tricarboxylic acid cycle and glyoxylate bypass in Mycobacterium tuberculosis, and its application to assessment of drug targets?

Author

Vivek Kumar Singh; Indira Ghosh

Publisher

BioMed Central; Springer (Biomed Central Ltd.); [London]: BioMed Central, 2004-; Springer Science and Business Media LLC (ISSN 1742-4682)

Published

2006

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)