Figure 4. Intracellular bacteria co-opt or disrupt phagosomal lipid metabolism as a survival strategy.

M. tuberculosis secretes the glycosylated PI analog lipoarabinomannan (LAM) to inhibit the production of PI(3)P by Vps34 in addition to secreting the phosphatase SapM, which dephosphorylates PI(3)P. Together, these effectors decrease vacuolar PI(3)P to arrest phagosome maturation and produce a favorable intracellular niche for M. tuberculosis survival. S. enterica injects the effector SigD into the cell. This phosphatase depletes PI(4,5)P₂ from the plasma membrane, leading to bacterial invasion into the host cell. Once inside, SigD has been suggested to dephosphorylate PI(3,4,5)P₃ to produce PI(3)P. Alternatively, SigD products might modulate Vps34 in order to increase vacuolar PI(3)P. These effects help the bacterium divert the maturation of the invasion vacuole away from the conventional antimicrobial trajectory of phagosomes.