Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SIMoS, Gif-sur-Yvette, France.
Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Gif-sur-Yvette, France.
PLoS Negl Trop Dis. 2021 Mar 12;15(3):e0009231. doi: 10.1371/journal.pntd.0009231. eCollection 2021 Mar.
Salmonella and Shigella bacteria are food- and waterborne pathogens that are responsible for enteric infections in humans and are still the major cause of morbidity and mortality in the emerging countries. The existence of multiple Salmonella and Shigella serotypes as well as the emergence of strains resistant to antibiotics requires the development of broadly protective therapies. Recently, the needle tip proteins of the type III secretion system of these bacteria were successfully utilized (SipD for Salmonella and IpaD for Shigella) as vaccine immunogens to provide good prophylactic cross-protection in murine models of infections. From these experiments, we have isolated a cross-protective monoclonal antibody directed against a conserved region of both proteins. Its conformational epitope determined by Deep Mutational Scanning is conserved among needle tip proteins of all pathogenic Shigella species and Salmonella serovars, and are well recognized by this antibody. Our study provides the first in vivo experimental evidence of the importance of this common region in the mechanism of virulence of Salmonella and Shigella and opens the way to the development of cross-protective therapeutic agents.
沙门氏菌和志贺氏菌是食源性和水源性病原体，可导致人类肠道感染，仍是新兴国家发病率和死亡率的主要原因。多种沙门氏菌和志贺氏菌血清型的存在以及对抗生素的耐药菌株的出现，需要开发广泛保护的治疗方法。最近，成功利用了这些细菌的 III 型分泌系统的针尖蛋白（沙门氏菌的 SipD 和志贺氏菌的 IpaD）作为疫苗免疫原，在感染的小鼠模型中提供了良好的预防性交叉保护。从这些实验中，我们分离出了一种针对两种蛋白保守区域的交叉保护型单克隆抗体。通过深度突变扫描确定的其构象表位在所有致病性志贺氏菌种和沙门氏菌血清型的针尖蛋白中保守，并被该抗体很好地识别。我们的研究提供了关于该共同区域在沙门氏菌和志贺氏菌毒力机制中的重要性的第一个体内实验证据，并为开发交叉保护治疗剂开辟了道路。
