REGULATION OF CAPSULE SYNTHESIS IN A PATHOGENIC E. COLI ISOLATE

致病性大肠杆菌分离株中胶囊合成的调控

• 批准号: 3790850
• 负责人: T A RUSSO
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3790850
• 关键词: Escherichia coli; bacterial capsules; bacterial polysaccharides; bactericidal immunity; carbohydrate biosynthesis; gene complementation; molecular cloning; regulatory gene; virulence

We have determined that capsular polysaccharide of a K54 clinical isolate of Escherichia coli is an important virulence factor. Capsular antigens in E. coli can be divided into two groups on the basis of microbiologic, physical and chemical characteristics. Group 1 capsules are associated with non-pathogens whereas, group 2 capsules are present in pathogenic extra-intestinal isolates. An understanding of group 2 capsular regulation may lead to novel therapeutic approaches, therefore we have undertaken studies in this area. Group 1 capsule regulators have been identified and cloned. We have examined by complementation, gene disruption and gene fusion experiments what effect they had on the group 2 capsules of our K54 clinical isolate. Genes for both group 1 and 2 capsular polysaccharide are present and are non-allelic. The group 1 positive regulators RcsA and B stimulate group 1 capsule production but apparently not group 2. A group 1 negative regulator, ion protease, either directly or indirectly decreases group 2 gene transcription. This decrease in group 2 gene transcription is associated with an increased serum sensitivity. This is consistent with the protective effect of group 2 capsule against the bactericidal effects of serum. We are presently in the process of identifying and cloning the group 2 regulators genes which appear to be, at least in part, separate from the group 1 capsular regulatory genes.

我们已经确定K54临床的荚膜多糖 大肠杆菌分离株是一种重要毒力因子。荚膜 抗原E.大肠杆菌可分为两类， 微生物、物理和化学特性。第1组胶囊 与非病原体相关，而第2组胶囊存在 致病性肠外分离株中。对第二组的理解 因此，囊膜调节可能导致新的治疗方法， 我们已进行这方面的研究。第1组胶囊调节器具有 被识别和克隆。我们已经通过互补，基因 破坏和基因融合实验对群体有什么影响 2粒K54临床分离株胶囊。 第1组和第2组荚膜多糖的基因都存在， 非等位基因。第1组正性调节因子RcsA和B刺激组 1个胶囊生产，但显然不是第2组。A组1阴性 调节剂，离子蛋白酶，直接或间接地减少组2 基因转录第2组基因转录的减少是 与血清敏感性增加有关。这符合 组2胶囊对杀菌剂的保护作用 血清的影响。我们目前正在确认和 克隆第2组调节基因，这些基因似乎至少在 部分，独立于组1荚膜调控基因。