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Autophagy, an immunologic magic bullet: Mycobacterium tuberculosis phagosome maturation block and how to bypass it

Vojo Deretic

University of New Mexico Health Sciences Center, Department of Molecular Genetics & Microbiology, 915 Camino de Salud, NE, Albuquerque, NM 87131-001, USA.

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Email the corresponding author at vderetic@salud.unm.edu

Published Online:23 Sep 2008https://doi.org/10.2217/17460913.3.5.517

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Abstract

Mycobacterium tuberculosis is a facultative intracellular pathogen that parasitizes host macrophages where it persists in immature phagosomes by avoiding their maturation into phagolysosomes. The mechanisms of how M. tuberculosis inhibits phagolysosome biogenesis have been researched in detail and the maturation block at least partially depends on the manipulation of host phosphoinositide interconversions, with phosphatidylinositol 3-phosphate (PI3P) being a central target since it has been shown to be required for phagolysosome biogenesis. PI3P earmarks intracellular organelles for binding and assembly of effector molecules that interact with PI3P or its derivatives, including Class E Vps proteins such as Hrs and ESCRT components, early endosome antigen 1, which are required for sequential protein and membrane sorting within the endosomal and, by extension, phagosomal systems. In a search of a cellular mechanism that can bypass the tubercule bacillus-imposed PI3P block, researchers have uncovered a new general bactericidal process, autophagy, which can eliminate intracellular pathogens. This is a new, rapidly growing field replete with possibilities for novel, previously untried immunologic and pharmacologic interventions applicable not only to TB but to other stubborn bacterial, parasitic and viral diseases.

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Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.

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Vol. 3, No. 5

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Published online 23 September 2008

Published in print October 2008

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The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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