title: Mycobacterial escape from macrophage phagosomes to the cytoplasm represents an alternate adaptation mechanism.
abstract: Survival of Mycobacterium tuberculosis (Mtb) within the host macrophage is mediated through pathogen-dependent inhibition of phagosome-lysosome fusion, which enables bacteria to persist within the immature phagosomal compartment. By employing ultrastructural examination of different field isolates supported by biochemical analysis, we found that some of the Mtb strains were in fact poorly adapted for subsistence within endocytic vesicles of infected macrophages. Instead, through a mechanism involving activation of host cytosolic phospholipase A2, these bacteria rapidly escaped from phagosomes, and established residence in the cytoplasm of the host cell. Interestingly, by facilitating an enhanced suppression of host cellular autophagy, this translocation served as an alternate virulence acquisition mechanism. Thus, our studies reveal plasticity in the adaptation strategies employed by Mtb, for survival in the host macrophage.
authors.affiliation: Immunology Group International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Shilpa V
authors.initials: SV
authors.lastname: Jamwal
authors.affiliation: Immunology Group International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Parul
authors.initials: P
authors.lastname: Mehrotra
authors.affiliation: Systems Biology Group Institute of Genomics and Integrative Biology, Mall Road, New Delhi, 110007, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Singh
authors.affiliation: Immunology Group International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Zaved
authors.initials: Z
authors.lastname: Siddiqui
authors.affiliation: National Institute of Virology Dr. Babasaheb Ambedkar Road, Pune, 411001, India.
authors.forename: Atanu
authors.initials: A
authors.lastname: Basu
authors.affiliation: Immunology Group International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Kanury V S
authors.initials: KV
authors.lastname: Rao
mesh_terms: D000222:Adaptation, Physiological / Q000276:immunology*; D001343:Autophagy / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003593:Cytoplasm / Q000276:immunology* / Q000382:microbiology / Q000648:ultrastructure; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D057131:Immune Evasion / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology / Q000648:ultrastructure; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D010587:Phagocytosis / Q000276:immunology; D010588:Phagosomes / Q000276:immunology* / Q000382:microbiology / Q000648:ultrastructure; D054510:Phospholipases A2, Cytosolic / Q000276:immunology / Q000378:metabolism; D022161:Transport Vesicles / Q000276:immunology / Q000382:microbiology / Q000648:ultrastructure; D014774:Virulence / Q000276:immunology
chemical_list: D054510:Phospholipases A2, Cytosolic