Unit for Molecular Glycobiology, VIB Department for Molecular Biomedical Research, Ghent University, Technologiepark 927, 9052 Ghent, Belgium.
Biochem Soc Trans. 2011 Jan;39(1):349-54. doi: 10.1042/BST0390349.
FimH is the type 1 fimbrial tip adhesin and invasin of Escherichia coli. Its ligands are the glycans on specific proteins enriched in membrane microdomains. FimH binding shows high-affinity recognition of paucimannosidic glycans, which are shortened high-mannose glycans such as oligomannose-3 and -5. FimH can recognize equally the (single) high-mannose glycan on uroplakin Ia, on the urinary defence protein uromodulin or Tamm-Horsfall glycoprotein and on the intestinal GP2 glycoprotein present in Peyer's patches. E. coli bacteria may attach to epithelial cells via hundreds of fimbriae in a multivalent fashion. This binding is considered to provoke conformational changes in the glycoprotein receptor that translate into signalling in the cytoplasm of the infected epithelial cell. Bladder cell invasion by the uropathogenic bacterium is the prelude to recurrent and persistent urinary tract infections in humans. Patients suffering from diabetes mellitus are more prone to contract urinary tract infections. In a study of women, despite longer treatments with a more potent antibiotic, these patients also have more often recurrences of urinary tract infections compared with women without diabetes. Type 1 fimbriae are the most important virulence factors used not only for adhesion of E. coli in the urinary tract, but also for the colonization by E. coli in patients with Crohn's disease or ulcerative colitis. It appears that the increased prevalence of urinary tract infections in diabetic women is not the result of a difference in the bacteria, but is due to changes in the uroepithelial cells leading to an increased adherence of E. coli expressing type 1 fimbriae. Hypothetically, these changes are in the glycosylation of the infected cells. The present article focuses on possible underlying mechanisms for glycosylation changes in the uroepithelial cell receptors for FimH. Like diabetes, bacterial adhesion induces apoptosis that may bring the endoplasmic reticulum membrane with immature mannosylated glycoproteins to the surface. Indicatively, clathrin-mediated vesicle trafficking of glucose transporters is disturbed in diabetics, which would interfere further with the biosynthesis and localization of complex N-linked glycans.
FimH 是大肠杆菌的 1 型菌毛尖端黏附素和侵袭素。它的配体是富含在膜微区中的特定蛋白上的聚糖。FimH 结合表现出对寡甘露糖的高亲和力识别，寡甘露糖是缩短的高甘露糖聚糖，例如寡甘露糖-3 和 -5。FimH 可以平等地识别尿路上皮蛋白 uroplakin Ia 上的（单个）高甘露糖聚糖、尿防御蛋白 uromodulin 或 Tamm-Horsfall 糖蛋白以及派尔集合淋巴结中存在的肠 GP2 糖蛋白上的高甘露糖聚糖。大肠杆菌细菌可以通过数百个菌毛以多价方式附着到上皮细胞上。这种结合被认为会引起糖蛋白受体的构象变化，从而转化为受感染上皮细胞细胞质中的信号转导。尿路致病性细菌对膀胱细胞的侵袭是人类复发性和持续性尿路感染的前奏。患有糖尿病的患者更容易患尿路感染。在一项对女性的研究中，尽管接受了更长时间、更有效的抗生素治疗，但与没有糖尿病的女性相比，这些患者的尿路感染复发频率更高。1 型菌毛是最重要的毒力因子，不仅用于大肠杆菌在尿路中的黏附，也用于克罗恩病或溃疡性结肠炎患者的大肠杆菌定植。似乎糖尿病女性尿路感染的高发率不是由于细菌的差异，而是由于尿路上皮细胞的变化导致表达 1 型菌毛的大肠杆菌的黏附增加。从理论上讲，这些变化存在于受感染细胞的糖基化中。本文重点介绍了 FimH 受体尿路上皮细胞糖基化变化的潜在机制。与糖尿病一样，细菌黏附会诱导细胞凋亡，可能会将不成熟的甘露糖基化糖蛋白的内质网膜带到表面。有迹象表明，糖尿病患者葡萄糖转运蛋白的网格蛋白介导的囊泡运输受到干扰，这将进一步干扰复杂 N 连接聚糖的生物合成和定位。
