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In particular, the metabolic challenges faced by intracellular pathogens, such as<jats:italic>Mycobacterium tuberculosis<\/jats:italic>, residing in the infected host provide novel opportunities for therapeutic intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We developed a mathematical framework to simulate the effects on the growth of a pathogen when enzymes in its metabolic pathways are inhibited. Combining detailed models of enzyme kinetics, a complete metabolic network description as modeled by flux balance analysis, and a dynamic cell population growth model, we quantitatively modeled and predicted the dose-response of the 3-nitropropionate inhibitor on the growth of<jats:italic>M. tuberculosis<\/jats:italic>in a medium whose carbon source was restricted to fatty acids, and that of the 5'-<jats:italic>O<\/jats:italic>-(<jats:italic>N<\/jats:italic>-salicylsulfamoyl) adenosine inhibitor in a medium with low-iron concentration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The predicted results quantitatively reproduced the experimentally measured dose-response curves, ranging over three orders of magnitude in inhibitor concentration. Thus, by allowing for detailed specifications of the underlying enzymatic kinetics, metabolic reactions\/constraints, and growth media, our model captured the essential chemical and biological factors that determine the effects of drug inhibition on<jats:italic>in vitro<\/jats:italic>growth of<jats:italic>M. tuberculosis<\/jats:italic>cells.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1752-0509-3-92","type":"journal-article","created":{"date-parts":[[2009,9,16]],"date-time":"2009-09-16T06:13:38Z","timestamp":1253081618000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["A systems biology framework for modeling metabolic enzyme inhibition of Mycobacterium tuberculosis"],"prefix":"10.1186","volume":"3","author":[{"given":"Xin","family":"Fang","sequence":"first","affiliation":[]},{"given":"Anders","family":"Wallqvist","sequence":"additional","affiliation":[]},{"given":"Jaques","family":"Reifman","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2009,9,15]]},"reference":[{"key":"360_CR1","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1146\/annurev.genom.2.1.343","volume":"2","author":"T Ideker","year":"2001","unstructured":"Ideker T, Galitski T, Hood L: A new approach to decoding life: systems biology. 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