Analysis of Campylobacter coli Lipooligosaccharide Core Diversity

描述（由申请方提供）：弯曲杆菌是美国胃肠炎的最重要原因，也是发展中国家旅行者腹泻的常见原因。少量但显著数量的弯曲杆菌感染也与格林巴利综合征（GBS）的发展有关。据信，GBS是由于弯曲杆菌糖脂、脂寡糖（LOS）的外核上的唾液酸糖残基与人神经节苷脂的碳水化合物部分之间的分子模拟而触发的。 LOS已被证明是参与与弯曲杆菌介导的感染和GBS相关的重要过程的许多毒力因子之一。关于LOS核心寡糖的生物合成及其在食源性致病菌-大肠弯曲杆菌中的致病作用的研究较少。该提议的广泛的长期目标是进一步了解弯曲杆菌LOS的组装以及存在于各种弯曲杆菌物种中的LOS的结构多样性在发病机制中所起的作用。具体目标我将集中在表征的LOS生物合成位点从C。大肠杆菌Penner血清菌株。具体目标II将重点分析C。大肠杆菌LOS核心寡糖的多样性。具体目标III将集中于C.大肠杆菌突变体参与LOS的生物合成。本提案的具体目标将利用涉及分子生物学和细菌遗传学技术的实验进行，这些实验可以很容易地由本科生和研究生研究人员进行。此外，该提案中的研究有望导致开发出更灵敏的所有C的检测方法。大肠杆菌的血清型，并提供了深入了解的组织和功能的核心寡糖的LOS在食源性病原体，C。杆菌

DESCRIPTION (provided by applicant): Campylobacter is the most important cause of gastroenteritis in the United States and a frequent cause of traveler's diarrhea in developing countries. A small but significant number of Campylobacter infections have also been linked to the development of Guillain Barre Syndrome (GBS). It is believed that GBS is triggered as a result of molecular mimicry between the sialic acid sugar residues on the outer core of the Campylobacter glycolipid, lipooligosaccharide (LOS) and the carbohydrate moiety of human gangliosides. LOS has been shown to be one of many virulence factors involved in important processes associated with Campylobacter-mediated infection and GBS. Little attention has been given for studies on the biosynthesis of the core oligosaccharide of LOS and its role in pathogenesis in the emerging food borne pathogen, Campylobacter coli. The broad, long term objective of this proposal is to further understand the assembly of the Campylobacter LOS and the role that structural diversity of the LOS, which exists among various Campylobacter species, plays in pathogenesis. Specific Aim I will focus on characterization of the LOS biosynthetic loci from C. coli Penner serostrains. Specific Aim II will focus on an analysis of C. coli LOS core oligosaccharide diversity among clinical isolates. Specific Aim III will focus on the genetic analysis of C. coli mutants involved in the biosynthesis of LOS. The specific aims in this proposal will be carried out utilizing experiments involving techniques of molecular biology and bacterial genetics that can be easily performed by both undergraduate and graduate student researchers. Furthermore, the studies in this proposal are expected to lead to the development of a more sensitive detection method of all C. coli serotypes present in clinical isolates and offer insights into the organization and function of the core oligosaccharide of LOS in the food borne pathogen, C. coli.