OMVs produced by E. coli bacteria responsible for sepsis cause the accumulation of autophagosomes in host cells. Confocal microscopy image of HeLa cells with autophagosomes in green, OMVs in red, and nuclei in blue.
France is strongly committed to the fight against sepsis[1]. The Ministry of Solidarity and Health, in collaboration with learned societies and the patient association France Sepsis Association, is carrying out several projects aimed at improving the monitoring of cases of sepsis in the territory, public knowledge of the sepsis, training of healthcare professionals, prevention, screening and treatment of sepsis.
The “Pathogeny and commensalism of enterobacteriaceae” team of the Digestive Health Research Institute (IRSD – Inserm / INRAE / ENVT / CHU / UT3 Paul Sabatier) led by Prof. Oswald is carrying out research in this direction. Their results show that in the fight against sepsis, it is not only necessary to kill the bacteria in question, but also to reduce their capacity to produce vesicles. a few tens of nanometers (called OMV for Outer Membrane Vesicle in English). For this, it is necessary to act directly upstream on the mechanisms of production of these nanoparticles and/or by developing therapeutic strategies to eliminate them. The team has in fact shown that these OMVs are very harmful for the host, and could promote the aggravation of sepsis. These results were published in the scientific journal Autophagy.
Sepsis is an acute state of dysregulation of the body’s response to an infection (bacterial, viral, fungal or parasitic) leading to the loss of organ function, which compromises the survival of the patient. It is estimated each year that more than 50 million people worldwide are affected by sepsis and nearly 11 million the number of deaths. Escherichia coli is one of the bacteria most frequently responsible for these infections.
These bacteria can produce large amounts of OMVs. These bioparticles are insensitive to antibiotic treatments and have a high capacity for dissemination. The IRSD research team (Inserm / INRAE / ENVT / CHU / UT3 Paul Sabatier) has shown that an overproduction of OMVs is linked to the production of a protein, HlyF, expressed by these E. coli pathogens.
This research carried out by the scientists has also shown that these OMVs inhibit autophagy, an important mechanism for cell survival. This inhibition leads to the establishment of an excessive inflammatory state in the cells of the infected patient. Since autophagy and inflammation are crucial in the host response to infection, especially during sepsis, these research results revealed an unsuspected role of OMVs in the exacerbated pathogenic properties of these bacteria.
[1] Sepsis is a life-threatening disease characterized by a maladaptive host response to infection and organ failure