Abstract
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 Statement
The authors have declared no competing interest.
- Abbreviations
- AIEC
- adherent-invasive E. coli
- BDI
- Bright Detail Intensity
- BMDM
- bone marrow-derived macrophages
- Casp
- Caspase
- E. coli
- Escherichia coli
- EHEC
- enterohemorrhagic E. coli
- ExPEC
- extra-intestinal pathogenic E. coli
- GSDM-D
- Gasdermin-D
- GFP
- Green Fluorescent Protein
- HBSS
- Hanks’balanced salt solution
- HlyF
- Hemolysin F
- IL-1β
- interleukin-1β
- ISX
- ImageStreamX system
- LPS
- Lipopolysaccharide
- OMV
- outer membrane vesicle
- RFP
- Red Fluorescent Protein
- TEM
- transmission electron microscopy
- WT
- Wild type
- Mut
- Mutated