Fatty Acid Catabolism &the glyoxylate shunt in Mycobact

Cornell University Ithaca, Ithaca NY

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Abstract

Description (adapted from the application): Isocitrate lyase (Icl) the first enzyme of the glyoxylate pathway is upregulated in M. tuberculosis when it is exposed to reduced oxygen tension or when exposed to an intracellular environment of activated macrophages. Icl competes with the Ich enzyme diverting the carbon from TCA cycle, which is otherwise wasted. The investigators suggest that Icl may utilize fatty acids found within the macrophages when they become the limiting carbon sources that explain their up-regulation and thus explain a probable mechanism by which M. tuberculosis can survive within hostile macrophages. The role of Icl in the pathogenesis of tuberculosis will be investigated under three specific aims of a funded RO1 grant addressing respectively the environmental inducers of Icl, role of Icl in maintaining latent infection and identifying inhibitors of Icl. This grant application will focus on identifying the substrates that feed the glyoxylate pathway using M. smegmatis and what this pathway does for the bacterium.