Outer membrane vesicles produced by pathogenic strains of

Autor: Laure, David, Frédéric, Taieb, Marie, Pénary, Pierre-Jean, Bordignon, Rémi, Planès, Salimata, Bagayoko, Valérie, Duplan-Eche, Etienne, Meunier, Eric, Oswald
Rok vydání: 2023
Předmět:
Zdroj: Autophagy
ISSN: 1554-8635
Popis: 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
Databáze: OpenAIRE