Lack of Acidification in Mycobacterium Phagosomes Produced by Exclusion of the Vesicular Proton-ATPase

Abstract

The success of Mycobacterium species as pathogens depends on their ability to maintain an infection inside the phagocytic vacuole of the macrophage. Although the bacteria are reported to modulate maturation of their intracellular vacuoles, the nature of such modifications is unknown. In this study, vacuoles formed around Mycobacterium avium failed to acidify below pH 6.3 to 6.5. Immunoelectron microscopy of infected macrophages and immunoblotting of isolated phagosomes showed that Mycobacterium vacuoles acquire the lysosomal membrane protein LAMP-1, but not the vesicular proton-adenosine triphosphatase (ATPase) responsible for phagosomal acidification. This suggests either a selective inhibition of fusion with proton-ATPase-containing vesicles or a rapid removal of the complex from Mycobacterium phagosomes.

Characterization and intracellular trafficking pattern of vacuoles containing Chlamydia pneumoniae in human epithelial cells

“…A similar result has been obtained for C. trachomatis, which also does not reside in an acidic compartment (Heinzen et al, 1996;Schramm et al, 1996). Although the mechanism of how Cpn prevents acidi®cation is not known, the exclusion of the proton pump H -ATPase from the inclusion is the proposed mechanism of C. trachomatis (Heinzen et al, 1996) and M. tuberculosis (Sturgill-Koszycki et al, 1994). The proton pump HATPase is acquired from organelles of the endocytic cascade during maturation.…”

Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

“…Together with phagosome acidification and lysosomal enzymes, these reactive intermediates constitute the effector mechanism by which macrophages combat resistant intracellular bacteria such as M. tuberculosis. The complexity of host-pathogen interactions is underlined by the recent demonstration that virulent mycobacteria maintain the phagolysosome as an habitable environment by preventing normal vacuole acidification through the exclusion of the vesicular proton-ATPase [50].…”

Human V-ATPase gene can protect or predispose the host to pulmonary tuberculosis

“…The pathogen inhibits phagosome maturation excluding V-ATPase from the phagosome. 6,7 Bafilomycin A 1 (an inhibitor of V-ATPase) reduces significantly the intracellular killing of phagocytosed M tuberculosis 8 and the production of reactive oxygen species. 8 Both these activities contribute significantly to the antimicrobial activity of the phagocytic cell.…”