Mycobacterium marinum antagonistically induces an autophagic response while repressing the autophagic flux in a TORC1- and ESX-1-dependent manner

Article Article scientifique Article Mycobacterium marinum antagonistically induces an autophagic response while repressing the autophagic flux in a TORC1- and ESX-1-dependent manner eng 2017 author Cardenal-Munoz Elena 819156 author Arafah Sonia 713749 author Lopez Jimenez Ana Teresa 734756 author Kicka Sébastien 736074 author Falaise Alexandra 677020 author Bach Frauke author Schaad Olivier 0000-0003-1576-783X 23118 author King Jason S author Hagedorn Monica 622357 author Soldati Thierry 0000-0002-2056-7931 135632 e1006344 10.1371/journal.ppat.1006344 28414774 1553-7366 Autophagy is a eukaryotic catabolic process also participating in cell-autonomous defence. Infected host cells generate double-membrane autophagosomes that mature in autolysosomes to engulf, kill and digest cytoplasmic pathogens. However, several bacteria subvert autophagy and benefit from its machinery and functions. Monitoring infection stages by genetics, pharmacology and microscopy, we demonstrate that the ESX-1 secretion system of Mycobacterium marinum, a close relative to M. tuberculosis, upregulates the transcription of autophagy genes, and stimulates autophagosome formation and recruitment to the mycobacteria-containing vacuole (MCV) in the host model organism Dictyostelium. Antagonistically, ESX-1 is also essential to block the autophagic flux and deplete the MCV of proteolytic activity. Activators of the TORC1 complex localize to the MCV in an ESX-1-dependent manner, suggesting an important role in the manipulation of autophagy by mycobacteria. Our findings suggest that the infection by M. marinum activates an autophagic response that is simultaneously repressed and exploited by the bacterium to support its survival inside the MCV. Autophagy Bacterial Proteins/genetics/metabolism Dictyostelium/genetics/metabolism/microbiology Host-Pathogen Interactions Humans Multiprotein Complexes/genetics/metabolism Mycobacterium Infections Nontuberculous/genetics/metabolism/physiopathology/virology Mycobacterium marinum/genetics/metabolism TOR Serine-Threonine Kinases/genetics/metabolism Vacuoles/microbiology Dewey 540 39 Département de biochimie 144 false 766 Groupe Soldati PLOS Pathogens 13 4 5a936805-5aa0-4c9f-b2dc-edab1009d870 Article (Published version) Public Cardenal-Muñoz et al17.pdf 1391841 application/pdf openAccess Faculté des sciences / Section de chimie et biochimie / Département de biochimie

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Mycobacterium marinum antagonistically induces an autophagic response while repressing the autophagic flux in a TORC1- and ESX-1-dependent manner	PLOS Pathogens			2017	548	467

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Falaise, Alexandra