Outer membrane vesicles produced by pathogenic strains ofEscherichia coliblock autophagic flux and exacerbate inflammasome activation

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.

Extracellular vesicles of the probiotic E. coli O83 activate innate immunity and prevent allergy in mice

“…They are produced during normal bacterial growth by detachment of the outer membrane and consist largely of outer membrane components such as lipopolysaccharide (LPS), lipids and proteins, but may also contain material from the periplasmic space or from within the bacterial cell, such as nucleic acids 20 . Several studies have investigated OMVs of pathogenic [21][22][23][24] or non-pathogenic [25][26][27] E. coli strains, but OMVs of E. coli O83 have not yet been investigated. OMVs contain microbe-associated molecular patterns that give them immunostimulatory properties.…”