SPATEs promote the survival of Shigella to the plasma complement system upon local hemorrhage and bacteremia

ABSTRACT: "Shigella spp. are the causative agents of shigellosis, which remains a major cause of death in children under the age of five. Shigellosis is marked by fever and leads to hemorrhagic diarrhea; Shigella bacteremia are reported in more severe cases. These clinical features strongly suggest that Shigella survive to plasma exposure, although it has not been previously investigated at a molecular level. In this report, we confirmed in a guinea pig model of shigellosis that local hemorrhages were induced by S. flexneri 5a and S. sonnei and we demonstrated that Shigella reached CD31+/CD34+ blood vessels within the mucosa during late infection stage and further disseminated in the blood circulation. These results confirmed the exposition of Shigella to plasma components during its virulence cycle, from the hemorrhagic colonic mucosa to the blood circulation. We demonstrated that all tested Shigella strains survived to plasma exposure in vitro and we have shown that Serine Protease Autrotransporters of Enterobacteriaceae (SPATEs) are essential for Shigella dissemination within the colonic mucosa and in the blood circulation. We confirmed that SPATEs were expressed and secreted within poorly oxygenated environments encountered by Shigella from hypoxic foci of infection to the blood circulation. We have further demonstrated that SPATEs promoted the survival of Shigella to plasma exposure, by cleaving the complement 3 component (C3), hence impairing the complement system activation."

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Johana Chicher  

LAB HEAD: Benoit Marteyn

PROVIDER: PXD048033 | Pride | 2024-08-27

REPOSITORIES: pride