Salmonella Typhi: Enhancement of Endemic Potential through its Unique Virulence Factors

项目摘要/摘要 伤寒是人类历史上最成功、最具破坏性的传染病之一。 这是一个严重的现实问题，每年导致20万人死亡，2100万人患病。致病因素 伤寒的致病菌是革兰氏阴性菌伤寒沙门氏菌(S.Typhi)，它适合于 只对人类有效。伤寒沙门氏菌的持续携带性感染状态，如“伤寒玛丽”，对 人与人之间的传播和细菌在人类体内的持续维持。如果我们要 有效控制和根除伤寒，我们需要实施抑制伤寒杆菌转化的战略 变为持续感染状态。然而，首先，我们必须了解伤寒沙门氏菌如何促进从急性 持续/携带性感染状态。在人性化的小鼠模型中，作为伤寒沙门氏菌的持久性 感染模型，伤寒毒素，一种独特的A2B5毒素或由伤寒杆菌胞内产生的外毒素，已被 被认为是促进伤寒沙门氏菌感染向持续携带转变的关键细菌决定因素 感染状态。在R01中，我们提出了一系列实验，以更好地了解伤寒毒素介导的 促进伤寒沙门氏菌持续感染的宿主细胞相互作用机制。拟议的研究可能会提供 制定有效的干预策略以更好地控制伤寒沙门氏菌的关键信息 传播和暴发。

PROJECT SUMMARY/ABSTRACT Typhoid fever is one of the most successful and devastating infectious diseases in human history and remains a serious real-world problem that kills 0.2 million and sickens 21 million people every year. The etiological agent of typhoid fever is the gram-negative bacterium Salmonella enterica serovar Typhi (S. Typhi), which is adapted solely to humans. S. Typhi’s persistent-carriage infection state, exemplified by “Typhoid Mary,” is critical for person-to-person transmission and the continued maintenance of the bacterium within humans. If we are to effectively contain and eradicate typhoid fever, we need to implement strategies inhibiting S. Typhi’s transition to the persistent infection state. First, however, we must understand how S. Typhi facilitates transition from acute to a persistent/carriage infection state. In a humanized mouse model that serves as a S. Typhi’s persistent infection model, typhoid toxin, a distinct A2B5 toxin or exotoxin produced by intracellular S. Typhi, has been identified as a critical bacterial determinant facilitating the transition of S. Typhi infection to the persistent-carriage infection state. In this R01, we propose a series of experiments to better understand the typhoid toxin-mediated host cell interactive mechanism promoting S. Typhi’s persistent infection. The proposed research may provide critical information for the development of efficacious intervention strategies to better control S. Typhi’s transmission and outbreaks.