Phenotype MicroArray Analysis of Fastidious Pathogens

项目描述（由申请人提供）：该项目的主要目标是将biologic， Inc （Hayward， CA）的“表型微阵列”（Phenotype MicroArray[TM]）（“PM”）技术应用于挑剔和嗜微气细菌物种，特别强调那些对人类疾病重要的细菌。PM技术可以高效、灵敏地表征微生物细胞的数千种生理和表型特性。这里提出的I期研究将集中在胃病原体幽门螺杆菌（Hp）（与消化性溃疡疾病和胃癌有关）和肠道病原体空肠弯曲杆菌（Cj）（胃肠炎和类风湿关节炎的常见病因，以及（某些菌株）自身免疫诱导的周围神经变性和瘫痪-格林-巴利综合征）。Cj和惠普的基因各不相同。在群体遗传结构中，Cj是弱克隆的，而Hp被认为是非克隆的，但在基因库中表现出显著的地理差异，特别是东亚、欧洲和美洲的菌株。第一期str项目有两个实验目的。

DESCRIPTION (provided by applicant): The principal goal of this project is to adapt the "Phenotype MicroArray[TM]" ("PM") technology of Biolog, Inc (Hayward, CA) for fastidious and microaerophilic bacterial species, with special emphasis on those important in human disease. PM technology allows efficient, sensitive characterization of thousands of physiologic and phenotypic properties of microbial cells. The Phase I studies proposed here will focus on strains of the gastric pathogen Helicobacter pylori (Hp) (implicated in peptic ulcer disease and gastric cancer), and the intestinal pathogen Campylobacter jejuni (Cj) (a very common cause of gastroenteritis, and rheumatoid arthritis, and also (with some strains) of an autoimmune induced peripheral nerve degeneration and paralysis - Guillain Barre syndrome). Cj and Hp are each genetically diverse. Cj is weakly clonal in population genetic structure, whereas Hp is considered non-clonal, but exhibits striking geographic differences in gene pools, especially with strains of East Asia vs. Europe and the Americas. This Phase I STTR project has two experimental Aims. First: To refine, optimize, and implement a PM technology testing protocol for robust analysis of representative Hp and Cj strains. This will make testing of Hp and Cj strains available to the scientific research community, either through PM Kits or PM Services. Second: To transfer this technology to Berg's lab, where it will be beta site tested and used to study a range of Hp and Cj strains chosen primarily for their particular disease associations and to assess if such disease associations are linked to metabolic differences or other PM-detected phenotypic traits. With Hp, the effects of human gastrin (a reported stimulator of Hp growth, and possible signal of Hp entry into the gastric mucosa) on PM profiles will be determined. With Cj, PM profiles of representative strains will be scored at 37C vs. 42C, to assess if thermal signaling might be used by Cj to adapt to different hosts (human vs. chicken). In Phase II the PM methodology will be implemented for representative strains of other Helicobacter and Campylobacter species, and also for other genera of fastidious pathogens.