New type of functional heterogeneity with urinary p* E. coli fimbriae adhesin

目的：用原位法研究食蟹猴肾至阴道内黏附素介导的大肠杆菌与泌尿生殖组织结合受体的表达。研究了四种相关黏附素的特异性受体- p -纤维膜上与gal-α(1-4)gal鞘糖脂（分别优先为glob糖苷和Forssman抗原）结合的PapG和PrsG，以及1型纤维膜上的两种FimH变体，一种与单甘露糖/三甘露糖结合，另一种仅与三甘露糖结合。为了确定观察到的结合的特异性，我们使用了受体类似物和大肠杆菌粘附素敲除突变体的粘附抑制作用。猴子组织中PapG和FimH受体的分布与人类有很大的相似之处。猴膀胱和输尿管表面有单甘露糖受体表达，而天马糖受体则不表达。大肠杆菌中FimH同工受体的不同分布和FimH黏附素变异的异质性可能解释了早期在1型膜介导的人膀胱和肾组织黏附中相互矛盾的发现。我们还发现了在阴道和尿道粘膜上存在一种迄今未知类型的宿主-攻击者相互作用的证据，直到1型菌毛被清除后才发现。热受体和细菌凝集素之间的精确分子匹配在感染发病机制中是重要的。由于大肠杆菌粘附素受体在两种动物上皮表面的表达相似，我们得出结论，食蟹猴的尿路感染是人类疾病的相关模型。

Objective: To study the expression of receptors allowing adhesin mediated binding of Escherichia coli to urogenital tissues from kidney to vagina in cynomolgus monkeys, using an in situ assay.M&M. Receptors specific for four relevant adhesins were investigated - PapG and PrsG of P-fimbriae binding to gal-α(1-4)gal glycosphingolipids (preferentially globoside and the Forssman antigen respectively) and two variants of FimH of type 1 fimbriae one binding to monomannose/trimannose and the other to trimannose only. To asccertain the specificity of the observed bindings we used adhesion inhibition by receptor analogues as well as E. coli adhesin knock out mutants.Results. The distribution of PapG and FimH receptors in monkey tissues showed great similarities to available data in humans. While monomanose receptors were expressed on surface epithelium both in the monkey bladder and ureter timannose receptors were not. The different distribution of FimH isoreceptors and the heterogeneity of FimH adhesin variants among E. coli may explain contradictory earlier findings in type 1 fimbrae mediated adhesion to the human bladder and to renal tissues. We also found evidence of a hetherto unknown type of host-aggressor interaction on vaginal and urethral mucosae, not uncovered until type 1 fimbriae had been eliminated.Conclusions. A precise molecular fit between hot receptors and bacterial lectins is important in infectious pathogenesis. We conclude that UTI in the cynomolgous monkey is a relevant model of the human disease because of the similarity in expression of receptors for E. coli adhesins on epithelial surfaces in the two species.