Outer membrane vesicles produced by pathogenic strains of Escherichia coli block autophagic flux and exacerbate inflammasome activation.
Autophagy
; 18(12): 2913-2925, 2022 12.
Article
en En
| MEDLINE
| ID: mdl-35311462
ABSTRACT
Escherichia coli strains are responsible for a majority of human extra-intestinal infections, resulting in huge direct medical and social costs. We had previously shown that HlyF encoded by a large virulence plasmid harbored by pathogenic E. coli is not a hemolysin but a cytoplasmic enzyme leading to the overproduction of outer membrane vesicles (OMVs). Here, we showed that these specific OMVs inhibit the macroautophagic/autophagic flux by impairing the autophagosome-lysosome fusion, thus preventing the formation of acidic autolysosomes and autophagosome clearance. Furthermore, HlyF-associated OMVs were more prone to activate the non-canonical inflammasome pathway. Because autophagy and inflammation are crucial in the host's response to infection especially during sepsis, our findings revealed an unsuspected role of OMVs in the crosstalk between bacteria and their host, highlighting the fact that these extracellular vesicles have exacerbated pathogenic properties.Abbreviations AIEC adherent-invasive E. coliBDI bright detail intensityBMDM bone marrow-derived macrophagesCASP caspaseE. coli Escherichia coliEHEC enterohemorrhagic E. coliExPEC extra-intestinal pathogenic E. coliGSDMD gasdermin DGFP green fluorescent proteinHBSS Hanks' balanced salt solutionHlyF hemolysin FIL1B/IL-1B interleukin 1 betaISX ImageStreamX systemLPS lipopolysaccharideMut mutatedOMV outer membrane vesicleRFP red fluorescent proteinTEM transmission electron microscopyWT wild-type.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Escherichia coli
/
Infecciones por Escherichia coli
Límite:
Humans
Idioma:
En
Revista:
Autophagy
Año:
2022
Tipo del documento:
Article
País de afiliación:
Francia