Figure 4.

Mtb senses and responds to its redox environment. Hypoxia, gasotransmitters and lipid metabolism saturate the electron transport chain and electron carriers within the cell, inducing reductive stress (left). Elements responsive to reductive stress (left) execute a coordinated output, involving fatty acids synthesis to counter reductive stress and inhibit aspects of the immune response, expression of proteins important in the induction of dormancy, and decreasing the expression of highly antigenic secretion systems. On the other end of the spectrum, increased oxygen, the presence of numerous anti-TB drugs, and the respiratory burst of host phagocytes (right) can induce intracellular oxidative stress and ROI capable of damaging DNA, lipids and proteins. EGT and MSH can protect the cell by detoxifying ROI, promoting survival and resistance to drugs. WhiB proteins respond by upregulating the expression of secretion systems ESX-2 and ESX-4 (right). Ultimately, the ability of Mtb to sense and respond to a dynamic redox environment during infection is essential for Mtb virulence and pathogenesis.