SPATEs promote the survival ofto the plasma complement system upon local hemorrhage and bacteremia.

Abstract

spp. are the causative agents of shigellosis, which remains a leading cause of death in children under the age of 5. Symptoms of shigellosis include bloody diarrhea, associated to colon hemorrhage; in more severe casesbacteremia is induced. These clinical features indicate thatare exposed and survive exposure to plasma, locally and systemically, although this has not yet been studied at a molecular level. In this report, we confirmed in a guinea pig model of shigellosis that both5a andinduced local hemorrhages and we demonstrated thatreached CD31+/CD34+ blood vessels located in the mucosa during the late stages of infection, and further disseminated in the bloodstream. These results confirmed the exposure ofto plasma components during its virulence cycle. We demonstrated that all the testedstrains survived plasma exposure in vitro, and we showed that Serine Protease Autotransporters of Enterobacteriaceae (SPATEs) contribute todissemination within the colonic mucosa and in the bloodstream. We have confirmed that SPATEs are expressed and secreted in poorly oxygenated environments encountered byduring late infection stages. We further demonstrated that SPATEs promotedsurvival in plasma, by cleaving complement component 3 (C3), thereby impairing the complement system activation. We have shown here that the ability ofto survive plasma exposure is a key factor in its virulence, both within primary foci and systemically.