IF 11.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science Advances Pub Date : 2025-01-31
Philippe N. Azimzadeh, George M. Birchenough, Nathaniel C. Gualbuerto, Jerome S. Pinkner, Kevin O. Tamadonfar, Wandy Beatty, Thomas J. Hannan, Karen W. Dodson, Enid C. Ibarra, Seonyoung Kim, Henry L. Schreiber 4th, James W. Janetka, Andrew L. Kau, Ashlee M. Earl, Mark J. Miller, Gunnar C. Hansson, Scott J. Hultgren
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摘要

尿路感染(UTI)的复发率很高,而且经常是由病人肠道中的致尿路感染大肠杆菌(UPEC)菌株引起的。这种肠道菌株进入泌尿道很可能是导致UTI复发(rUTI)的原因之一。因此,了解促进 UPEC 肠道定植的因素对于设计降低 rUTI 发病率的疗法至关重要。虽然大肠杆菌大量存在于大肠粘液中,但人们对其如何在这种持续分泌的水凝胶中保持定植却知之甚少。我们发现,1 型纤毛的 FimH 黏附因子(T1P)与整个结肠分泌粘液层以及小鼠和人体样本中的上皮细胞结合。破坏 T1P 会导致与结肠粘液的结合减少。值得注意的是,这种突变体上调了鞭毛的产生,并渗入结肠的保护性内粘液层。这可以解释 UPEC 如何抵御结肠持续分泌的粘液层的冲刷。
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Mechanisms of uropathogenic E. coli mucosal association in the gastrointestinal tract
Urinary tract infections (UTIs) are highly recurrent and frequently caused by Uropathogenic Escherichia coli (UPEC) strains that can be found in patient intestines. Seeding of the urinary tract from this intestinal reservoir likely contributes to UTI recurrence (rUTI) rates. Thus, understanding the factors that promote UPEC intestinal colonization is of critical importance to designing therapeutics to reduce rUTI incidence. Although E. coli is found in high abundance in large intestine mucus, little is known about how it is able to maintain residence in this continuously secreted hydrogel. We discovered that the FimH adhesin of type 1 pili (T1P) bound throughout the secreted mucus layers of the colon and to epithelial cells in mouse and human samples. Disruption of T1P led to reduced association with colon mucus. Notably, this mutant up-regulated flagellar production and infiltrated the protective inner mucus layer of the colon. This could explain how UPEC resists being washed off by the continuously secreted mucus layers of the colon.
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来源期刊
Science Advances
Science Advances 综合性期刊-综合性期刊
CiteScore
21.40
自引率
1.50%
发文量
1937
审稿时长
29 weeks
期刊介绍: Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.
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