Modulation of cellular phosphatidylinositol 3-phosphate levels in primary macrophages affects heat-killed but not viable Mycobacterium avium's transport through the phagosome maturation process

Cellular Microbiology
Victoria A Kelley, Jeffrey S Schorey

Abstract

Most disease causing mycobacteria are intramacrophage pathogens which replicate within nonacidified phagosomes that can interact with the early endosomal network but fail to mature to a phagolysosome. The mycobacterial phagosome retain some proteins required for fusion with endocytic vesicles including Rab5 but lack others such as early endosomal autoantigen 1 (EEA1). As the membrane lipid phosphatidylinositol 3-phosphate (PtdIns-3-P) is required for EEA1 membrane association and phagosome maturation, it may be a potential target of pathogenic mycobacteria. To test this hypothesis, macrophage cellular levels of PtdIns-3-P were altered by retroviral introduction of the type III Phosphoinositide 3-Kinase (VPS34) and the PtdIns-3-P phosphatase myotubularin 1 (MTM1). By utilizing the PtdIns-3-P-specific probes FYVE and PX coupled to EGFP (EGFP-2-FYVE and EGFP-PX, respectively), the expression of PtdIns-3-P on the mycobacterial phagosome was addressed. All phagosomes containing viable Mycobacterium avium stained positive for EGFP-2-FYVE and EGFP-PX despite obvious differences in PtdIns-3-P concentrations in cells expressing MTM1 or VPS34. Altering PtdIns-3-P cellular concentrations did not affect trafficking of live bacilli. However...Continue Reading

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Citations

Dec 8, 2007·Microbiology and Molecular Biology Reviews : MMBR·John H Brumell, Marci A Scidmore
Mar 28, 2008·Cellular Microbiology·Sofia AxelrodUlrich E Schaible
Jan 13, 2006·Current Opinion in Microbiology·Edith N G HoubenJean Pieters
Jun 20, 2006·Current Opinion in Cell Biology·Tony YeungSergio Grinstein
Apr 5, 2014·Current Protocols in Immunology·Christine SteinhäuserNorbert Reiling

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