PT - JOURNAL ARTICLE AU - Laure David AU - Frédéric Taieb AU - Marie Pénary AU - Pierre-Jean Bordignon AU - Rémi Planès AU - Valérie Duplan-Eche AU - Etienne Meunier AU - Eric Oswald TI - Outer membrane vesicles produced by pathogenic strains of <em>Escherichia coli</em> block autophagic flux and exacerbate inflammasome activation AID - 10.1101/2021.04.20.440604 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.04.20.440604 4099 - http://biorxiv.org/content/early/2021/04/20/2021.04.20.440604.short 4100 - http://biorxiv.org/content/early/2021/04/20/2021.04.20.440604.full AB - Escherichia coli (E. coli) strains are responsible for a majority of human extra-intestinal infections, resulting in huge medical, economic 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 show that these specific OMVs inhibit the autophagic flux by impairing the autophagosome – lysosome fusion, thus preventing the formation of acidic autolysosome and autophagosome clearance. Furthermore, OMVs from E. coli producing HlyF are much more prone to activate the non-canonical inflammasome pathway. Since autophagy and inflammation are crucial in the host’s response to infection especially during sepsis, our findings reveal an unsuspected role of OMVs in the crosstalk between bacteria and their host, highlighting the fact that these extracellular vesicles have exacerbated pathogenic properties compared to OMVs produced by isogenic strains unable to produce a functional HlyF.Competing Interest StatementThe authors have declared no competing interest.AbbreviationsAIECadherent-invasive E. coliBDIBright Detail IntensityBMDMbone marrow-derived macrophagesCaspCaspaseE. coliEscherichia coliEHECenterohemorrhagic E. coliExPECextra-intestinal pathogenic E. coliGSDM-DGasdermin-DGFPGreen Fluorescent ProteinHBSSHanks’balanced salt solutionHlyFHemolysin FIL-1βinterleukin-1βISXImageStreamX systemLPSLipopolysaccharideOMVouter membrane vesicleRFPRed Fluorescent ProteinTEMtransmission electron microscopyWTWild typeMutMutated