Mycobacterium marinum antagonistically induces an autophagic response while repressing the autophagic flux in a TORC1- and ESX-1-dependent manner.
PLoS Pathog
; 13(4): e1006344, 2017 Apr.
Article
em En
| MEDLINE
| ID: mdl-28414774
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Proteínas de Bactérias
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Mycobacterium marinum
/
Complexos Multiproteicos
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Serina-Treonina Quinases TOR
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Infecções por Mycobacterium não Tuberculosas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
PLoS Pathog
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Suíça