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

PLoS Pathogens

Monica Hagedorn¹  Jason S. King²  Olivier Schaad³  Ana Teresa López-Jiménez³  Alexandra Falaise³  Sonia Arafah³  Sébastien Kicka³  Elena Cardenal-Muñoz³  Frauke Bach⁴  Thierry Soldati⁴ 

[1] Bateson Centre, University of Sheffield, Firth Court, Western Bank, Sheffield, United Kingdom;Centre for Membrane Interactions and Dynamics, Department of Biomedical Sciences, University of Sheffield, Firth Court, Western Bank, Sheffield, United Kingdom;Department of Biochemistry, Faculty of Sciences, Sciences II, University of Geneva, Geneva, Switzerland;Section Parasitology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany

关键词: Dictyostelium discoideum;    Autophagic cell death;    Lysosomes;    Mycobacterium tuberculosis;    Immunoblotting;    Secretion systems;    Intracellular pathogens;    Cytosol;   

DOI  :  10.1371/journal.ppat.1006344

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY