How uromodulin helps flush out bacteria Urinary tract infections (UTIs) are one of the most frequent bacterial infections in humans. The glycoprotein uromodulin is the most abundant urinary protein and can provide some protection from UTIs, but the precise mechanism has been unclear. Weiss et al. found that uromodulin forms stacked, fishbone-like filaments that act as a multivalent decoy for bacterial pathogens with adhesive pili that attach to the uromodulin glycans (see the Perspective by Kukulski). The resulting uromodulin-pathogen aggregates prevent bacterial adhesion to glycoproteins of the urinary epithelium and promote pathogen clearance as urine is excreted. This innate protection against UTIs is likely to be particularly important in infants and children. Science, this issue p. 1005; see also p. 917 Uromodulin filaments in human urine associate with uropathogens and mediate bacterial aggregation and clearance. Uromodulin is the most abundant protein in human urine, and it forms filaments that antagonize the adhesion of uropathogens; however, the filament structure and mechanism of protection remain poorly understood. We used cryo–electron tomography to show that the uromodulin filament consists of a zigzag-shaped backbone with laterally protruding arms. N-glycosylation mapping and biophysical assays revealed that uromodulin acts as a multivalent ligand for the bacterial type 1 pilus adhesin, presenting specific epitopes on the regularly spaced arms. Imaging of uromodulin-uropathogen interactions in vitro and in patient urine showed that uromodulin filaments associate with uropathogens and mediate bacterial aggregation, which likely prevents adhesion and allows clearance by micturition. These results provide a framework for understanding uromodulin in urinary tract infections and in its more enigmatic roles in physiology and disease.

中文翻译：

---

尿路感染中人尿调节蛋白丝的结构和功能

尿调节蛋白如何帮助清除细菌 尿路感染 (UTI) 是人类最常见的细菌感染之一。糖蛋白尿调节蛋白是最丰富的尿蛋白，可以提供一定程度的保护以防止 UTI，但其确切机制尚不清楚。韦斯等人。发现尿调节蛋白形成堆叠的鱼骨状细丝，作为细菌病原体的多价诱饵，具有附着在尿调节蛋白聚糖上的粘附菌毛（参见 Kukulski 的观点）。由此产生的尿调制素-病原体聚集体可防止细菌粘附到尿上皮的糖蛋白上，并在尿液排出时促进病原体清除。这种针对 UTI 的先天保护可能对婴儿和儿童尤其重要。科学，这个问题 p。1005; 另见第 917 人尿中的尿调制素丝与尿路病原体相关并介导细菌聚集和清除。尿调节蛋白是人体尿液中含量最丰富的蛋白质，它形成细丝，拮抗泌尿病原体的粘附；然而，对灯丝结构和保护机制仍知之甚少。我们使用冷冻电子断层扫描显示尿调制素丝由具有横向突出臂的锯齿形骨架组成。N-糖基化图谱和生物物理测定表明尿调节蛋白作为细菌 1 型菌毛粘附素的多价配体，在规则间隔的臂上呈现特定的表位。体外和患者尿液中尿调节素-尿路病原体相互作用的成像显示尿调节素丝与尿路病原体相关并介导细菌聚集，这可能会防止粘连并允许通过排尿清除。这些结果为理解尿路感染中的尿调节蛋白及其在生理学和疾病中更神秘的作用提供了一个框架。