Enterics

低感染剂量内源性致病菌的检测、致病机理及疫苗学 研究项目五包括三个子项目，侧重于基因组学的关键新方面， 三种主要B类低剂量肠道病原菌的致病机理和疫苗学研究 在临床和环境样本中进行检测。其中包括高度耐氯的隐孢子虫 细小杆菌，最可怕的志贺氏菌威胁(志贺氏菌1)和基本上无法治疗的志贺氏菌毒素 肠出血性肠出血性肠杆菌这三种病原菌在低感染剂量下都有严重的风险。 生物恐怖主义的诱因以及国家和全球重大的卫生、地方病和流行病挑战。这个 该项目的研究团队在与这些生物体合作方面有着非常出色的记录。领头羊 在肠道疾病方面具有国际声誉的经验丰富的调查人员，Richard L.Guerrant和James B.Kaper，这个项目建立在高生产率的专业知识和长期的和新的跨机构基础上 UVA、UMD、VCU、VT、USUHS、UVT和JHU的协同效应。 我们的第一个子项目V.1，关于“隐孢子虫基因组学、致病机理和疫苗学”建立 在VCU小组对人类(1型)微小弧菌基因组进行接近完成的测序后， 以植物为基础的UVA组织发表了隐孢子虫的组织培养、动物和现场经验 VT黏膜疫苗的生产和UVA，UVT，UVT， 和JHU用于鉴定和表达1型(人)微小弧菌候选基因，确定它们在 发病机制和免疫，表达有希望的候选者，并定义人类的遗传决定因素 因此，疫苗开发的最佳方法。子项目V.2将使用UMD， USUHS和UVA的同事构建了新型志贺氏菌和肠出血性大肠杆菌(EHEC) 疫苗和开发新的肠出血性肠出血性疾病治疗方法。子项目V.3将产生额外的 用于检测人类粪便对水(可能还有食物)污染的诊断“可交付物” 三种低感染剂量B类肠道病原体的特异性检测 肠学计划的重点是细小葡萄球菌、痢疾杆菌和肠出血性肠出血性大肠杆菌。

Low Infectious Dose Entropathogens: Detection, Pathogenesis and Vaccinology Research Project V includes three Sub-Projects focused on key new aspects of the genomics, pathogenesis and vaccinology of the three leading Category B low-dose enteropathogens, and on their detection in clinical and environmental samples. These include the highly chlorine-resistant Cryptosporidium parvum, the most fearsome Shigella threat (S. dysenteriae 1) and the largely untreatable, Shiga toxinproducing enterohemorrhagic E. coil These three pathogens all pose serious risks as low infectious dose agents of bioterrorism as well as major national and global health endemic and epidemic challenges. The team of investigators for this project has a very strong track record of working with these organisms. Led by experienced investigators with international reputations in enteric diseases, Richard L. Guerrant and James B. Kaper, this project builds upon highly productive expertise and upon longstanding and new crossinstitutional synergies at UVa, UMd, VCU, VT, USUHS, UVt, and JHU. Our first Sub-Project V.1, on "Cryptosporidium genomics, pathogenesis and vaccinology" builds upon the near complete sequencing of the human (type 1) C. parvum genome by the VCU group, the published tissue culture, animal and field experience with Cryptosporidium by the UVa group, the plantbased production of mucosal vaccines at VT and on studies of the genetics of susceptibility at UVa, UVt, and JHU to identify and express type 1 (human) C. parvum candidate genes, define their roles in pathogenesis and immunity, express promising candidates and define genetic determinants of human susceptibility and thus optimal approaches to vaccine development. Sub-Project V.2 will engage UMd, USUHS and UVa colleagues to construct novel Shigella dysenteriae and enterohemorrhagic E. coli (EHEC) vaccines and develop novel therapeutics for EHEC disease. Sub-Project V.3 will produce additional diagnostic "deliverables" for detection of human fecal contamination of water (and possibly food) as well as the specific detection of the three low infectious dose category B enteropathogens on which our RCE Enterics Program is focused, C. parvum, S. dysenteriae and EHEC.