The SapM phosphatase can arrest phagosome maturation in an ESX-1 independent manner in and BCG.

() is an intracellular pathogen that survives and grows in macrophages. A mechanism used by to achieve intracellular survival is to secrete effector molecules that arrest the normal process of phagosome maturation. Through phagosome maturation arrest (PMA), remains in an early phagosome and avoids delivery to degradative phagolysosomes. One PMA effector of is the secreted SapM phosphatase. Because the host target of SapM, phosphatidylinositol-3-phosphate (PIP), is located on the cytosolic face of the phagosome, SapM needs to not only be released by the mycobacteria but also travel out of the phagosome to carry out its function. To date, the only mechanism known for molecules to leave the phagosome is phagosome permeabilization by the ESX-1 secretion system. To understand this step of SapM function in PMA, we generated identical in-frame mutants in both the attenuated bacille Calmette-Guérin (BCG) vaccine strain, which lacks the ESX-1 system, and . Characterization of these mutants demonstrated that SapM is required for PMA in BCG and . Further, by establishing a role for SapM in PMA in BCG, and subsequently in a mutant lacking the ESX-1 system, we demonstrated that the role of SapM does not require ESX-1. We further determined that ESX-2 or ESX-4 is also not required for SapM to function in PMA. These results indicate that SapM is a secreted effector of PMA in both BCG and , and that it can function independent of the known mechanism for molecules to leave the phagosome.