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Comparative proteomics of uropathogenic Escherichia coli during growth in human urine identify UCA-like (UCL) fimbriae as an adherence factor involved in biofilm formation and binding to uroepithelial cells

机译:尿液致病性大肠杆菌在人尿生长过程中的比较蛋白质组学鉴定出UCA样(UCL)菌毛是参与生物膜形成并与尿道上皮细胞结合的粘附因子

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摘要

Uropathogenic Escherichia coli (UPEC) are the primary cause of urinary tract infection (UTI) in humans. For the successful colonisation of the human urinary tract, UPEC employ a diverse collection of secreted or surface-exposed virulence factors including toxins, iron acquisition systems and adhesins. In this study, a comparative proteomic approach was utilised to define the UPEC pan and core surface proteome following growth in pooled human urine. Identified proteins were investigated for subcellular origin, prevalence and homology to characterised virulence factors. Fourteen core surface proteins were identified, as well as eleven iron uptake receptor proteins and four distinct fimbrial types, including type 1, P, F1C/S and a previously uncharacterised fimbrial type, designated UCA-like (UCL) fimbriae in this study. These pathogenicity island (PAI)-associated fimbriae are related to UCA fimbriae of Proteus mirabilis, associated with UPEC and exclusively found in members of the E. coli B2 and D phylogroup. We further demonstrated that UCL fimbriae promote significant biofilm formation on abiotic surfaces and mediate specific attachment to exfoliated human uroepithelial cells. Combined, this study has defined the surface proteomic profiles and core surface proteome of UPEC during growth in human urine and identified a new type of fimbriae that may contribute to UTI.
机译:尿毒原性大肠杆菌(UPEC)是人类尿路感染(UTI)的主要原因。为了成功地将人尿道定殖,UPEC使用了多种分泌或表面暴露的毒力因子,包括毒素,铁捕获系统和粘附素。在这项研究中,比较蛋白质组学的方法被用来定义人类合并尿液中UPEC泛和核心表面蛋白质组。研究了鉴定出的蛋白质的亚细胞起源,普遍性以及与特征毒力因子的同源性。鉴定了14种核心表面蛋白,以及11种铁摄取受体蛋白和4种不同的纤维类型,包括1型,P,F1C / S和以前未表征的纤维类型,在本研究中称为UCA样(UCL)纤维。这些与致病岛(PAI)相关的菌毛与奇异变形杆菌的UCA菌毛有关,与UPEC有关,并且仅在大肠杆菌B2和D phylogroup成员中发现。我们进一步证明,UCL菌毛可促进非生物表面上显着的生物膜形成,并介导脱落的人尿道上皮细胞的特异性附着。综合起来,这项研究确定了人类尿液中UPEC的表面蛋白质组学特征和核心表面蛋白质组,并鉴定了可能有助于UTI的新型菌毛。

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