SPATEs promote the survival of <i>Shigella</i> to the plasma complement system upon local hemorrhage and bacteremia.

Abstract

<i>Shigella</i> 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 cases<i>, Shigella</i> bacteremia is induced. These clinical features indicate that <i>Shigella</i> are 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 both <i>S. flexneri</i> 5a and <i>S. sonnei</i> induced local hemorrhages and we demonstrated that <i>Shigella</i> reached 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 of <i>Shigella</i> to plasma components during its virulence cycle. We demonstrated that all the tested <i>Shigella</i> strains survived plasma exposure in vitro, and we showed that Serine Protease Autotransporters of Enterobacteriaceae (SPATEs) contribute to <i>Shigella</i> dissemination within the colonic mucosa and in the bloodstream. We have confirmed that SPATEs are expressed and secreted in poorly oxygenated environments encountered by <i>Shigella</i> during late infection stages. We further demonstrated that SPATEs promoted <i>Shigella</i> survival in plasma, by cleaving complement component 3 (C3), thereby impairing the complement system activation. We have shown here that the ability of <i>Shigella</i> to survive plasma exposure is a key factor in its virulence, both within primary foci and systemically.