Wurpel Daniël J, Totsika Makrina, Allsopp Luke P, Webb Richard I, Moriel Danilo G, Schembri Mark A
Australian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
J Proteomics. 2016 Jan 10;131:177-189. doi: 10.1016/j.jprot.2015.11.001. Epub 2015 Nov 3.
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.
尿路致病性大肠杆菌(UPEC)是人类尿路感染(UTI)的主要病因。为了成功定殖于人类尿路,UPEC利用多种分泌型或表面暴露的毒力因子,包括毒素、铁获取系统和黏附素。在本研究中,采用比较蛋白质组学方法来定义UPEC在混合人尿中生长后的泛表面蛋白质组和核心表面蛋白质组。对鉴定出的蛋白质进行亚细胞起源、普遍性以及与已鉴定毒力因子的同源性研究。鉴定出14种核心表面蛋白,以及11种铁摄取受体蛋白和4种不同类型的菌毛,包括1型、P型、F1C/S型以及一种先前未鉴定的菌毛类型,本研究中将其命名为UCA样(UCL)菌毛。这些与致病岛(PAI)相关的菌毛与奇异变形杆菌的UCA菌毛相关,与UPEC有关,且仅在大肠杆菌B2和D系统发育群的成员中发现。我们进一步证明,UCL菌毛可促进在非生物表面形成大量生物膜,并介导与脱落的人尿道上皮细胞的特异性黏附。综合来看,本研究定义了UPEC在人尿中生长期间的表面蛋白质组概况和核心表面蛋白质组,并鉴定出一种可能导致UTI的新型菌毛。