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

项目总结/摘要 伤寒是人类历史上最成功和最具破坏性的传染病之一， 这是一个严重的现实世界问题，每年造成20万人死亡，2100万人患病。病原 伤寒的病原体是革兰氏阴性细菌伤寒沙门氏菌（S.伤寒），这是适应 只对人类开放S.伤寒的持续携带感染状态，例如"伤寒玛丽"， 人与人之间的传播和细菌在人体内的持续维持。如果我们要 有效控制和消灭伤寒，我们需要实施抑制S.伤寒转变 持续感染状态首先，我们必须了解S。伤寒易从急性 持续/携带感染状态。在作为S.伤寒持续性 感染模型、伤寒毒素、由细胞内S.伤寒，已经 被鉴定为促进S.伤寒感染对持续带菌 感染状态。在这个R01中，我们提出了一系列的实验，以更好地了解伤寒毒素介导的 宿主细胞相互作用机制促进S.伤寒持续感染。这项研究可能提供 为制定有效的干预策略以更好地控制S.伤寒 传播和爆发。

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.