Glycosuria Alters Uropathogenic Escherichia coli Global Gene Expression and Virulence.
Glycosuria Alters Uropathogenic Escherichia coli Global Gene Expression and Virulence.
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尿路致病性大肠杆菌（UPEC）是糖尿病患者中一半以上尿路感染（UTI）的主要病原体。流行病学数据和上行性UTI小鼠模型的研究已经阐明了导致糖尿病宿主对UPEC-UTI易感性增加的各种宿主因素。相比之下，糖尿病尿微环境介导的UPEC生理学改变及其对糖尿病UPEC-UTI发病机制的影响尚未研究。为了解决我们的核心假设，即糖尿直接诱导UPEC的尿毒力，我们比较了人UPEC菌株UTI 89（膀胱炎）和CFT 073（肾盂肾炎）的毒力特征和基因表达，在体外暴露于来自男性或女性供体的尿液2小时，这些尿液是纯的或补充有葡萄糖以模拟糖尿。与暴露于营养丰富的培养基（溶原肉汤）的对照UPEC相比，暴露于糖尿的UPEC表现出生物膜形成的显著增加和豚鼠红细胞血凝的减少（1型纤毛的测量）。此外，通过RNA测序对UTI 89转录组的分析显示，2小时长的体外暴露于糖尿也显著改变了UPEC尿毒力的核心毒力和代谢基因的表达。添加半乳糖作为替代碳源影响UPEC的生物膜形成和基因表达谱的程度与葡萄糖暴露所观察到的相似。总之，我们的研究结果提供了新的见解如何糖尿病介导的UPEC健身的快速变化可能有助于UTI的发病机制在糖尿病尿微环境。重要性尿路致病性大肠杆菌（UPEC）是糖尿病患者尿路感染的重要病原体。我们研究了体外暴露于糖尿（尿液中存在葡萄糖）对UPEC毒力和基因表达的影响。我们的研究结果表明，糖尿迅速（2小时）改变UPEC基因表达，诱导生物膜形成，并抑制1型纤毛。这些结果为尿路UPEC的发病机制提供了新的见解。
Uropathogenic Escherichia coli (UPEC) is the principal etiology of more than half of urinary tract infections (UTI) in humans with diabetes mellitus. Epidemiological data and studies in mouse model of ascending UTI have elucidated various host factors responsible for increasing the susceptibility of diabetic hosts to UPEC-UTI. In contrast, diabetic urinary microenvironment-mediated alterations in UPEC physiology and its contributions to shaping UPEC-UTI pathogenesis in diabetes have not been examined. To address our central hypothesis that glycosuria directly induces urinary virulence of UPEC, we compared virulence characteristics and gene expression in human UPEC strains UTI89 (cystitis) and CFT073 (pyelonephritis), exposed for 2 h in vitro to urine from either male or female donors that was either plain or supplemented with glucose to mimic glycosuria. Compared to control UPEC exposed to nutrient-rich culture medium, lysogeny broth, glycosuria-exposed UPEC exhibited significant increase in biofilm formation and reduction in the hemagglutination of Guinea pig erythrocytes (a measure of type 1 piliation). In addition, the analysis of UTI89 transcriptome by RNA sequencing revealed that 2-h-long, in vitro exposure to glycosuria also significantly alters expression of virulence and metabolic genes central to urinary virulence of UPEC. Addition of galactose as an alternative carbon source affected biofilm formation and gene expression profile of UPEC to an extent similar to that observed with glucose exposure. In summary, our results provide novel insights into how glycosuria-mediated rapid changes in UPEC fitness may facilitate UTI pathogenesis in the diabetic urinary microenvironment. IMPORTANCE Uropathogenic Escherichia coli (UPEC) is an important causative agent of urinary tract infections in diabetic humans. We examined the effects of in vitro exposure to glycosuria (presence of glucose in urine) on the virulence and gene expression by UPEC. Our results show that glycosuria rapidly (in 2 h) alters UPEC gene expression, induces biofilm formation, and suppresses type 1 piliation. These results offer novel insights into the pathogenesis of UPEC in the urinary tract.
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DOI：
10.1046/j.1365-2362.2000.00745.x
发表时间：
2000-11-01
影响因子：
5.5
作者：
Geerlings, SE;Brouwer, EC;Hoepelman, AIM
通讯作者：
Hoepelman, AIM
影响因子：
16.2
作者：
Geerlings, SE;Meiland, R;Hoepelman, AIM
通讯作者：
Hoepelman, AIM
影响因子：
4.4
作者：
Bagale, Kamal;Paudel, Santosh;Kulkarni, Ritwij
通讯作者：
Kulkarni, Ritwij
影响因子：
7.3
作者：
Barkai, Laszlo Jozsef;Sipter, Emese;Hosszufalusi, Nora
通讯作者：
Hosszufalusi, Nora
影响因子：
3.2
作者：
Folsom, James Patrick;Parker, Albert E.;Carlson, Ross P.
通讯作者：
Carlson, Ross P.