Architecture and function of human uromodulin filaments in urinary tract infections

doi:10.1126/science.aaz9866

GSTDTAP > 气候变化

DOI	10.1126/science.aaz9866
	Architecture and function of human uromodulin filaments in urinary tract infections
	Gregor L. Weiss; Jessica J. Stanisich; Maximilian M. Sauer; Chia-Wei Lin; Jonathan Eras; Dawid S. Zyla; Johannes Trück; Olivier Devuyst; Markus Aebi; Martin Pilhofer; Rudi Glockshuber
	2020-08-21
发表期刊	Science
出版年	2020
英文摘要	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][1]; see also p. [917][2] 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. [1]: /lookup/doi/10.1126/science.aaz9866 [2]: /lookup/doi/10.1126/science.abd7124
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/291224
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Gregor L. Weiss,Jessica J. Stanisich,Maximilian M. Sauer,et al. Architecture and function of human uromodulin filaments in urinary tract infections[J]. Science,2020.
APA	Gregor L. Weiss.,Jessica J. Stanisich.,Maximilian M. Sauer.,Chia-Wei Lin.,Jonathan Eras.,...&Rudi Glockshuber.(2020).Architecture and function of human uromodulin filaments in urinary tract infections.Science.
MLA	Gregor L. Weiss,et al."Architecture and function of human uromodulin filaments in urinary tract infections".Science (2020).