title: Mycobacterium tuberculosis Inhibits RAB7 Recruitment to Selectively Modulate Autophagy Flux in Macrophages.
abstract: Here we report a novel regulatory mechanism for autophagy-mediated degradation of Mycobacterium tuberculosis (Mtb) and specific strategy exploited by the virulent Mtb to evade it. We show while both avirulent (H37Ra) and virulent (H37Rv) mycobacteria could readily localize to autophagosomes, their maturation into autolysosomes (flux) was significantly inhibited by the latter strain. The inhibition of autophagy flux by the virulent strain was highly selective, as it did not perturb the basal autophagy flux in the macrophages. Selective inhibition of flux of Mtb-containing autophagosomes required virulence regulators PhoP and ESAT-6. We show that the maturation of Mtb-containing autophagosomes into autolysosomes required recruitment of the late endosome marker RAB7, forming the intermediate compartment amphisomes. Virulent Mtb selectively evaded their targeting to the amphisomes. Thus we report a crosstalk between autophagy and phagosome maturation pathway and highlight the adaptability of Mtb, manifested by selective regulation of autophagy flux.
authors.affiliation: Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Chandra
authors.affiliation: Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Swapnil
authors.initials: S
authors.lastname: Ghanwat
authors.affiliation: Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Sumit Kumar
authors.initials: SK
authors.lastname: Matta
authors.affiliation: Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Swati Seth
authors.initials: SS
authors.lastname: Yadav
authors.affiliation: Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.|Department of Microbiology and Cell Biology, Centre for Infectious Disease Research, Indian Institute of Sciences, Bangalore, 560012, India.
authors.forename: Mansi
authors.initials: M
authors.lastname: Mehta
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: Department of Microbiology and Cell Biology, Centre for Infectious Disease Research, Indian Institute of Sciences, Bangalore, 560012, India.
authors.forename: Amit
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: Dhiraj
authors.initials: D
authors.lastname: Kumar
mesh_terms: D001343:Autophagy; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins
chemical_list: D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D020691:rab GTP-Binding Proteins