Recent data indicate that the nutrients available to Mycobacterium tuberculosis (Mtb) inside its host cell are restricted in their diversity. Fatty acids and cholesterol appear more favored, however,their degradation can result in certain metabolic stresses. Their breakdown can generate propionyl-CoA, which gives riseto potentially toxic intermediates. Detoxification of propionyl-CoA relies on the activity of the methylcitrate cycle, themethylmalonyl pathway or incorporation of the propionyl-CoA into methyl-branched lipids in the cell wall. The current articleexplores carbon flux through these pathways, focusing primarily on those pathways responsible for the incorporation of propionyl-CoAinto virulence-associated cell wall lipids. Exploiting both genetic and biochemical rescue we demonstrate that these metabolicpressures are experienced by Mtb inside its host macrophage, and that the bacterium accesses host fatty acid stores. Themetabolism of these host lipids expands the acetyl-CoA pool and alleviates the pressure from propionyl-CoA. These data havemajor implications to our appreciation of central metabolism of Mtb during the course of infection.
Keywords: Mycobacterium; tuberculosis; cholesterol; propionate