FIGURE 8.

Model of assimilation of host lipids and fatty acids into methyl-branched Mtb virulence lipids. Mtb has access to both cholesterol and fatty acids from the macrophage host cell. Degradation of cholesterol expands the pool of propionyl-CoA, which can be used to fuel central metabolism and biosynthetic pathways. Accumulation of propionyl-CoA and/or products of the MCC may limit the generation of acetyl-CoA from pyruvate by inhibiting PDH activity. Inhibition of PDH activity places more pressure on the acetyl-CoA pool, which is utilized as malonyl-CoA for the assembly of Mtb cell wall lipids. Additionally, MB cell wall lipids can be built using n-acyl primers generated either from de novo synthesis or from preformed long chain fatty acids imported by the bacterium. The integration of these two- and three-carbon metabolic pathways is clearly critical to the growth of Mtb and its success within its host cell environment.