Figure 8.

Resistance of Mycobacterium tuberculosis to phagolysosome contents. M. tuberculosis inhibits acidification by preventing the accumulation of V-ATPase on the phagosome membrane (161), in part through the action of protein tyrosine phosphatase (PtpA) (162). The bacterial lipoprotein, Lprl, can inhibit the lytic activity of lysozyme (226). The secretion system Esx-3 (230, 231) and the MmpS4/S5 transporters (232) are required for biosynthesis and secretion of the siderophores mycobactins (Mbac) and carboxymycobactins (Cabac), which seize Fe²⁺ from host proteins, such as lactoferrin (233). Then, the transporter system irtAB takes Fe²⁺ from Fe²⁺-carboxymycobactin into the bacterium (234, 235). The type I NADH dehydrogenase (NDH-1) (227) and the Eis protein (228) inhibit the NADPH oxidase, preventing formation of ROS. Also, M. tuberculosis prevents the generation of NO^⋅ and apoptosis by interfering with EBP50, a scaffolding protein that controls the recruitment of iNOS at the membrane of phagosomes (229). In addition, M. tuberculosis alters the phagosome to divert host lipids for its own benefit through mce4, a cholesterol import system (236), and through accumulation of lipid bodies via the early secretory antigenic target-6 (ESAT-6) (237). The enzymes isocitrate lyases (ICLs) allow bacteria survival on even (acetate) and odd (propionate) chain fatty acids in lipid bodies (238).