ERIN CRC: Molecular Basis of Nontyphoidal Salmonella Emergence

描述(申请人提供)：沙门氏菌属。导致多种人类疾病，包括非伤寒沙门氏菌病或NTS。NTS可表现为胃肠炎、菌血症或携带性状态。在美国和发达国家，大多数NTS是一种自限性胃肠炎，通常是在特定疫情期间由受污染的食物引起的。相比之下，非洲的NTS越来越多地表现为没有胃肠炎的菌血症，并显示出人与人之间的传播。有证据表明，这可能部分归因于宿主人群的免疫状况，包括艾滋病毒和疟疾等共病感染和/或营养状况。华盛顿大学Erin CRC的目标将是通过阐明微生物、宿主和种群因素在疾病和携带状态中的作用来理解流行病学上的这种差异。将建立三个项目，以1)检查肯尼亚NTS临床病例的宿主/病原体多样性(Judd Walson，Pl)，2)阐明来自非洲和美国的沙门氏菌菌株致病性的基因和表型相关性(Sam Miller，Pi)，以及3)确定限制人类宿主NTS菌血症的免疫相关性和机制(Brad Cookson，Pi)。这些项目将通过一个行政核心的努力进行协调，该核心还将建立和管理一个试点项目方案。

DESCRIPTION (provided by applicant): Salmonella spp. cause a variety of human diseases, including nontyphoidal salmonellosis or NTS. NTS can present as a gastroenteritis, bacteremia, or a carriage state. Most NTS in the United States and developed nations occurs as a self-limited gastroenteritis, typically from contaminated food during specific outbreaks. In contrast, NTS in Africa is increasingly manifesting as a bacteremia without gastroenteritis, and shows human-to-human spread. Evidence suggests that this may be due in part to the immune status of the host populations, including comorbid infections such as HIV and malaria, and/or nutritional status. The goals of the ERIN CRC at the University of Washington will be to understand this difference in epidemiology by elucidating the contribution of microbial, host, and population factors in disease and carriage states. Three projects will be established to 1) examine host/pathogen diversity in clinical cases of NTS in Kenya (Judd Walson, Pl), 2) elucidate the genotypic and phenotypic correlates of pathogenicity in Salmonella strains from Africa and the United States (Sam Miller, PI) and 3) determine the immune correlates and mechanisms of limiting NTS bacteremia in the human host (Brad Cookson, PI). The projects will be coordinated through the efforts of an Administrative Core, which will also establish and manage a Pilot Project program.