title: Kinetics of phosphatidylinositol-3-phosphate acquisition differ between IgG bead-containing phagosomes and Mycobacterium tuberculosis-containing phagosomes.
abstract: A key aspect of Mycobacterium tuberculosis pathogenesis is the ability of the bacteria to survive within the host macrophage. A phagosome containing an IgG-coated bead matures into a lysosomal compartment as evidenced by a decrease in pH and an increased acquisition of hydrolytic enzymes. In contrast, when M. tuberculosis is phagocytosed, the maturation of the bacteria-containing phagosome is arrested, and the bacterium resides within a vacuole that retains characteristics of early endosomal compartments. M. tuberculosis-containing phagosomes are delayed in the recruitment of the early endosome autoantigen EEA1. Acquisition of EEA1 is dependent on the presence of phosphatidylinositol-3-phosphate (PI-3-P) generated by the kinase Vps34. We tested the hypothesis that delayed recruitment of EEA1 was due to altered kinetics of PI-3-P accumulation at the phagosomal membrane. Biochemical analysis of the phosphatidylinositol phosphates on M. tuberculosis-containing phagosomes revealed that PI-3-P acquisition was markedly retarded and reduced in comparison to IgG bead-containing phagosomes. Given the role these lipids play in the regulation of phagosome maturation these findings have implications with respect to the mechanisms behind the arrest of phagosome maturation.
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Georgiana E
authors.initials: GE
authors.lastname: Purdy
authors.forename: Róisín M
authors.initials: RM
authors.lastname: Owens
authors.forename: Linda
authors.initials: L
authors.lastname: Bennett
authors.forename: David G
authors.initials: DG
authors.lastname: Russell
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Butcher
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D008264:Macrophages; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D010587:Phagocytosis; D010588:Phagosomes / Q000276:immunology* / Q000382:microbiology* / Q000502:physiology; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D033921:Vesicular Transport Proteins
chemical_list: D007074:Immunoglobulin G; D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; C055525:phosphatidylinositol 3-phosphate