Université de Strasbourg, Institut de Biologie Moléculaire et Cellulaire (IBMC), Architecture et Réactivité de l'ARN, Strasbourg 67000, France.
Plateforme protéomique Strasbourg Esplanade FRC1589 du CNRS, Université de Strasbourg, Strasbourg 67000, France.
Proc Natl Acad Sci U S A. 2024 Nov 5;121(45):e2319951121. doi: 10.1073/pnas.2319951121. Epub 2024 Oct 30.
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 bacteremia is induced. These clinical features indicate that 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 5a and induced local hemorrhages and we demonstrated that 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 to plasma components during its virulence cycle. We demonstrated that all the tested strains survived plasma exposure in vitro, and we showed that Serine Protease Autotransporters of Enterobacteriaceae (SPATEs) contribute to dissemination within the colonic mucosa and in the bloodstream. We have confirmed that SPATEs are expressed and secreted in poorly oxygenated environments encountered by during late infection stages. We further demonstrated that SPATEs promoted survival in plasma, by cleaving complement component 3 (C3), thereby impairing the complement system activation. We have shown here that the ability of to survive plasma exposure is a key factor in its virulence, both within primary foci and systemically.
spp. 是志贺氏菌病的病原体,它仍然是 5 岁以下儿童死亡的主要原因。志贺氏菌病的症状包括血性腹泻,伴有结肠出血;在更严重的情况下,会引起菌血症。这些临床特征表明,尽管尚未在分子水平上进行研究,但 会暴露于血浆中并在局部和全身存活下来。在本报告中,我们在志贺氏菌病豚鼠模型中证实,5a 和 均可诱导局部出血,并且我们证明 在感染后期到达位于粘膜中的 CD31+/CD34+血管,并进一步在血液中传播。这些结果证实了 在其毒力周期中暴露于血浆成分。我们证明了所有测试的 菌株都能在体外耐受血浆暴露,并且我们表明肠杆菌科丝氨酸蛋白酶自转运体(SPATEs)有助于 在结肠粘膜和血液中传播。我们已经证实 SPATEs 在 感染后期遇到的低氧环境中表达和分泌。我们进一步证明 SPATEs 通过切割补体成分 3(C3)促进 在血浆中的存活,从而削弱补体系统的激活。我们在这里表明, 在耐受血浆暴露的能力是其毒力的关键因素,无论是在原发性病灶内还是全身性的。