PMID:22087003

Citation	Wong, D, Bach, H, Sun, J, Hmama, Z and Av-Gay, Y (2011) Mycobacterium tuberculosis protein tyrosine phosphatase (PtpA) excludes host vacuolar-H+-ATPase to inhibit phagosome acidification. Proc. Natl. Acad. Sci. U.S.A. 108:19371-6
Abstract	Mycobacterium tuberculosis (Mtb) pathogenicity depends on its ability to inhibit phagosome acidification and maturation processes after engulfment by macrophages. Here, we show that the secreted Mtb protein tyrosine phosphatase (PtpA) binds to subunit H of the macrophage vacuolar-H(+)-ATPase (V-ATPase) machinery, a multisubunit protein complex in the phagosome membrane that drives luminal acidification. Furthermore, we show that the macrophage class C vacuolar protein sorting complex, a key regulator of endosomal membrane fusion, associates with V-ATPase in phagosome maturation, suggesting a unique role for V-ATPase in coordinating phagosome-lysosome fusion. PtpA interaction with host V-ATPase is required for the previously reported dephosphorylation of VPS33B and subsequent exclusion of V-ATPase from the phagosome during Mtb infection. These findings show that inhibition of phagosome acidification in the mycobacterial phagosome is directly attributed to PtpA, a key protein needed for Mtb survival and pathogenicity within host macrophages.
Links	PubMed PMC3228452 Online version:10.1073/pnas.1109201108
Keywords	Cloning, Molecular; Genetic Vectors; Hydrogen-Ion Concentration; Microscopy, Fluorescence; Monocytes/metabolism; Mycobacterium tuberculosis/enzymology; Mycobacterium tuberculosis/pathogenicity; Phagosomes/chemistry; Phagosomes/metabolism; Protein Interaction Mapping; Protein Tyrosine Phosphatases/metabolism; Vacuolar Proton-Translocating ATPases/metabolism
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