Fig. 1.

The M. tuberculosis response to hypoxia.

The top cell depicts the status of several systems involved in key features of the hypoxic response including the status of the DosS/R regulon (off with bound molecular oxygen on DosS in red). The TCA cycle operating normally with glycolytic and lipolytic precursors and components of the terminal electron transport chain operating through the Cytochrome C oxidase (CCO) system and the NADH oxidase Nuo. The bottom cell represents the status of these same systems under hypoxic conditions. DosS has phosphorylated DosR which transcriptionally engages the “DosR” regulon. The TCA cycle operates in a bifurcated cycle through the glyoxylate shunt to reoxidize NADH coupled to the secretion of succinate and intracellular inclusions of triacylglycerols (TAG) accumulate. Reduction of NADH also occurs through the Cytochrome B/D oxidase (CBD) and Ndh which do not pump protons.