Mycobacterium tuberculosis and Mycobacterium avium modify the composition of the phagosomal membrane in infected macrophages by selective depletion of cell surface-derived glycoconjugates

The many niches and strategies used by pathogenic mycobacteria for survival within host macrophages

“…Such phagosomes systematically mature and fuse with lysosomes within 2-6 hours post-infection (Fig. 2D-F;de Chastellier et al, 1995;Clemens and Horwitz, 1995;de Chastellier and Thilo, 1997;Pietersen et al, 2004). Although other investigators did not reach such conclusions, their data are in good agreement with the above finding.…”

“…3C or 4A), as well as immunoelectron microscopy have indeed shown that in cultured macrophages M. tuberculosis was generally observed exclusively in membrane-bound compartments not only at early time points post-infection (Armstrong and d'Arcy Hart, 1971;Sturgill-Koszycki et al, 1994;Xu et al, 1994;Clemens and Horwitz, 1995;Russell et al, 1996;Clemens et al, 2002) but also at much later time points, i.e. between 6 and 9 days post-infection (Beatty et al, 2000;Pietersen et al, 2004). Likewise, bacilli were exclusively intra-phagosomal in macrophages from 11-day-old in vitro-grown granulomas, (Peyron et al, 2008), in lung mononuclear phagocytes within Mtbinfected mice (Moreira et al, 1997) and also in alveolar macrophages from patients with tuberculosis (Mwandumba et al, 2004).…”

“…2A and B; de Chastellier and Thilo, 1997;Pietersen et al, 2004). The close apposition is such that, during intra-phagosomal division, the phagosome membrane remains closely apposed to the bacterial cell wall down into the sites of septum formation, and this ultimately leads to the division of the phagosome ( Fig.…”

Reversible Lipid Accumulation and Associated Division Arrest of Mycobacterium avium in Lipoprotein-Induced Foamy Macrophages May Resemble Key Events during Latency and Reactivation of Tuberculosis

“…This indicated that the initial targeting and subsequent fusion process depended on specific effects caused by mycobacteria from within the phagosome across both bilayer membrane leaflets. Our previous work has shown that a prerequisite for mycobacteria to reside in nonmaturing phagosomes is that they maintain the phagosome membrane in close apposition to their surface all around (56,(63)(64)(65). The molecular basis for this close interaction is not known, but could provide the means to initiate fusion with LB and subsequently destabilize the relevant phospholipid layers and expose them to lipolytic attack.…”

“…This might explain the observed deformation of the phagosome membrane where mycobacterium-containing phagosomes were in close contact with host lipid bodies. Further evidence for a transbilayer action of mycobacteria through the phagosome membrane came from observations where LB fused with phagosomes that contained multiple mycobacteria and for which the phagosome membrane was partially prevented from being closely apposed to the mycobacterial surface (e.g., where the membrane spans the region between two adjacent bacteria [65]). In such cases, fusion was observed only at sites where a close apposition could nevertheless be maintained.…”