The ESCRT and autophagy machineries cooperate to repair ESX-1-dependent damage at the <i>Mycobacterium</i>-containing vacuole but have opposite impact on containing the infection

by Ana T. López-Jiménez, Elena Cardenal-Muñoz, Florence Leuba, Lilli Gerstenmaier, Caroline Barisch, Monica Hagedorn, Jason S. King, Thierry Soldati

Phagocytic cells capture and kill most invader microbes within the bactericidal phagosome, but some pathogens subvert killing by damaging the compartment and escaping to the cytosol. To prevent the leakage of pathogen virulence and host defence factors, as well as bacteria escape, host cells have to contain and repair the membrane damage, or finally eliminate the cytosolic bacteria. All eukaryotic cells engage various repair mechanisms to ensure plasma membrane integrity and proper compartmentalization of organelles, including the Endosomal Sorting Complex Required for Transport (ESCRT) and autophagy machineries. We show that during infection of Dictyostelium discoideum with Mycobacterium marinum, the ESCRT-I component Tsg101, the ESCRT-III protein Snf7/Chmp4/Vps32 and the AAA-ATPase Vps4 are recruited to sites of damage at the Mycobacterium-containing vacuole. Interestingly, damage separately recruits the ESCRT and the autophagy machineries. In addition, the recruitment of Vps32 and Vps4 to repair sterile membrane damage depends on Tsg101 but appears independent of Ca2+. Finally, in absence of Tsg101, M. marinum accesses prematurely the cytosol, where the autophagy machinery restricts its growth. We propose that ESCRT has an evolutionary conserved function to repair small membrane damage and to contain intracellular pathogens in intact compartments.

Tratto da: www.plos.org
Note sul Copyright: Articles and accompanying materials published by PLOS on the PLOS Sites, unless otherwise indicated, are licensed by the respective authors of such articles for use and distribution by you subject to citation of the original source in accordance with the Creative Commons Attribution (CC BY) license.

Lascia un commento

Il tuo indirizzo email non sarà pubblicato. I campi obbligatori sono contrassegnati *