ROLE OF BACTERIAL LECTINS IN KIDNEY DISEASES

细菌凝集素在肾脏疾病中的作用

• 批准号: 3243030
• 负责人: Bogdan J Nowicki
• 金额: $ 12.48万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3243030
• 关键词: Escherichia coli; antigen receptors; bacterial DNA; bacterial antigens; genetic strain; histochemistry /cytochemistry; image processing; interstitial cystitis; laboratory mouse; microorganism hemagglutinin; mutant; nucleic acid hybridization; pyelonephritis; transposon /insertion element; urinary tract infection

Cystitis is the most common entity of urinary tract diseases, accounting for 1% of all office visits in the USA. Cystitis may lead to pyelonephritis, which is one of the main causes of end stage kidney disease. Escherichia coli is the most common pathogen of human urinary tract infection (UTI). Association of bacterial properties and clinical form of infection led to the discovery of P fimbriae as a virulence factor in acute pyelonephritis. P adhesions mediate attachment of E. coli to Gal-Gal rich receptors in the kidney tissue. Inhibition of attachment protects the kidney from colonization. Despite several efforts, a similar association has not been described for cystitis and chronic (CHP) pyelonephritis. Our recent studies have demonstrated that 26% of cystitis-associated E. coli and 35% of chronic pyelonephritis-associated E. coli (unpublished) but only 6% of those from asymptomatic bacteriuria and acute pyelonephritis carry genes of another type of adhesion, called Dr hemagglutinin. Dr hemagglutinin may attach to Dr receptor in UT and thereby allow bacterial colonization. Inhibition of the tissue-adhesion interaction might protect UT against colonization by Dr+ E. coli and prevent UT. At this time the contribution of Dr hemagglutinin and Dr receptors to pathogenicity of cystitis and chronic pyelonephritis has not been well documented. The proposed research will: (1) determine the locations of Dr receptors in tissues from different mouse strains; (2) quantitate the Dr receptor content in tissues of selected mouse strains; (3) construct Dr negative mutant of the clinical E. coli strain IH 11128; (4) determine the relative capacity of the Dr negative IH 11128 and Dr positive parent strain to colonize UT in a mouse model of ascending UTI; (5) determine persistence and pathogenesis of UTI induced by Dr positive E. coli in order to develop a model of chronic pyelonephritis; (6) further characterize epidemiology and properties of Dr+ E. coli by genotypic and phenotypic analysis.

膀胱炎是泌尿道疾病中最常见的实体，占 占美国所有办公室访问量的 1%。 膀胱炎可能会导致 肾盂肾炎，是终末期肾病的主要原因之一 疾病。 大肠杆菌是人类泌尿道最常见的病原体 感染（尿路感染）。 细菌特性与临床形式的关联 感染导致发现 P 菌毛作为急性感染的毒力因子 肾盂肾炎。 P 粘附介导大肠杆菌与富含 Gal-Gal 的附着 肾组织中的受体。 抑制附着可以保护 肾脏免受定植。 尽管做出了一些努力，类似的协会 尚未描述膀胱炎和慢性（CHP）肾盂肾炎。 我们最近的研究表明，26% 的膀胱炎相关大肠杆菌。 大肠杆菌和 35% 的慢性肾盂肾炎相关大肠杆菌（未发表），但 只有 6% 的人患有无症状菌尿和急性肾盂肾炎 携带另一种类型的粘附基因，称为血凝素博士。 博士 血凝素可能附着在 UT 中的 Dr 受体上，从而允许细菌 殖民化。 抑制组织粘附相互作用可能会保护 UT 可以对抗 Dr+ 大肠杆菌的定植并预防 UT。 此时的 Dr 血凝素和 Dr 受体对致病性的贡献 膀胱炎和慢性肾盂肾炎尚未得到充分记录。 拟议的研究将：（1）确定 Dr 受体在 来自不同品系小鼠的组织； (2) 定量 Dr 受体 选定小鼠品系的组织中的含量； (3)构建负博士 临床大肠杆菌菌株 IH 11128 的突变体； (4)确定亲属关系 Dr 阴性 IH 11128 和 Dr 阳性亲本菌株的能力 在上行性尿路感染小鼠模型中定植 UT； (5)确定持久性 以及博士阳性大肠杆菌诱导尿路感染的发病机制 慢性肾盂肾炎模型； (6) 进一步表征流行病学 通过基因型和表型分析了解 Dr+ 大肠杆菌的特性。