PATHOGENIC VIBRIO--INTESTINAL MUCOSAL INTERACTIONS

腹泻病仍然是世界范围内人类发病的重要原因 和死亡率，在许多发展中国家可能是最常见的 死因了 导致传染病发病的一系列事件 细菌性大肠杆菌比以前认识到的更复杂， 涉及各种微生物属性或毒力的相互作用 属性，用于规避主机防御。 特别是 粘膜表面上的宿主-病原体相互作用， 肠道和其它粘膜病原体建立仍然主要 悬而未决 这项拟议的研究将增加我们对以下问题的认识： 病原体-宿主粘膜相互作用，重点是在很大程度上未探索 胃肠粘液分泌的作用。 致病性弧菌会 因为人们对这种毒素有着丰富的了解 以及霍乱弧菌的几个毒力决定因素， 认识到，但缺乏对其他致病性弧菌物种的了解 (non O-1霍乱弧菌、副溶血弧菌、河流弧菌），可产生 妇科疾病。 扫描电子显微镜将用于确定 与上皮或粘蛋白结合的单独贡献， 致病性弧菌与肠道微生物的体内相互作用 感染时的粘膜。 这些数据将用于帮助评估有效性 一些常用的体外“粘附测定”。 粘蛋白的可能作用 定殖期间的利用将通过测定 降低粘蛋白非利用菌株毒力的基础 本实验室分离的霍乱弧菌的表型， 负责野生型菌株利用粘蛋白的活性， 以及来自不同来源的纯化粘蛋白作为 霍乱弧菌和其他致病性弧菌的生长底物。 变化 在粘蛋白的流变特性中， 致病性弧菌也将被评估。 运动的作用（或 趋化性）作为可能的毒力因子，如对霍乱弧菌的建议， 其他致病性弧菌的检测结果 如果运动是一个 其他弧菌的毒力决定因子，鞭毛疫苗将是 以确定它们是否像霍乱弧菌鞭毛疫苗一样， 保护性免疫原

Diarrheal diseases remain a significant worldwide cause of human morbidity and mortality, and in many developing countries may be the most common cause of death. The series of events leading to pathogenesis in infectious bacterial diarrheas are more complex than previously appreciated and involve interactions of various microbial attributes, or virulence properties, for circumventing host defenses. Particularly, the host-pathogen interactions on mucosal surfaces that lead to successful establishment of enteric and other mucosal pathogens remain largely unresolved. The proposed study will increase our knowledge of pathogen-host mucosal interactions with emphasis on the largely unexplored roles of gastrointestinal mucin secretions. Pathogenic vibrios will be used because of the wealth of knowledge that has accumulated on the toxin and several virulence determinants of V. cholerae and the growing awareness, but lack of understanding, of other pathogenic Vibrio species (non O-1 V. cholerae, V. parahemolyticus, V. fluvialis) that can produce diarrheal disease. Scanning electron microscopy will be used to determine the separate contributions of association with the epithelium or mucin to the in vivo interactions of the pathogenic vibrios with the intestinal mucosa during infection. The data will be used to help assess the validity of some often used in vitro "adherence assays". The possible role of mucin utilization during colonization will be assessed by determination of the basis for the reduced virulence of strains of a mucin non-utilizing phenotype of V. cholerae isolated by our laboratory, the enzymatic activities responsible for utilization of mucin by the wild-type strains, and the ability of purified mucin from different sources to serve as a growth substrate for V. cholerae and the other pathogenic vibrios. Changes in the rheological properties of mucin as a consequence of interactions with pathogenic vibrios also will be assessed. The role of motility (or chemotaxis) as a possible virulence factor, as suggested for V. cholerae, will be determined for the other pathogenic vibrios. If motility is a virulence determinant for the other vibrios, flagellar vaccines will be produced to determine if they, like V. cholerae flagellar vaccines, are protective immunogens.