Work

Mechanism of phagolysosome biogenesis block by viable Mycobacterium tuberculosis

Year: 2005

Type: article

Abstract: Live Mycobacterium tuberculosis persists in macrophage phagosomes by interfering with phagolysosome biogenesis. Here, using four-dimensional microscopy and in vitro assays, we report the principal difference between phagosomes containing live and dead mycobacteria. Phosphatidylinositol 3-phosphate (PI3P), a membrane trafficking regulatory lipid essential for phagosomal acquisition of lysosomal constituents, is retained on phagosomes harboring dead mycobacteria but is continuously eliminated from phagosomes with live bacilli. We show that the exclusion of PI3P from live mycobacterial phagosomes can be only transiently reversed by Ca2+ fluxes, and that live M. tuberculosis secretes a lipid phosphatase, SapM, that hydrolyzes PI3P, inhibits phagosome-late endosome fusion in vitro, and contributes to inhibition of phagosomal maturation.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.0409716102

Authors: Isabelle Vergne, Jennifer Chua, Hwang-Ho Lee, Megan Lucas, John Belisle, Vojo Deretic

Institutions: University of New Mexico, University of New Mexico Health Sciences Center, Colorado State University

Language: English

Topic: Tuberculosis Research and Epidemiology

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute of Allergy and Infectious Diseases