Toval Francisco, Schiller Roswitha, Meisen Iris, Putze Johannes, Kouzel Ivan U, Zhang Wenlan, Karch Helge, Bielaszewska Martina, Mormann Michael, Müthing Johannes, Dobrindt Ulrich
Institute of Hygiene, University of Münster, Münster, Germany.
Institute of Hygiene, University of Münster, Münster, Germany Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany.
Infect Immun. 2014 Nov;82(11):4631-42. doi: 10.1128/IAI.01701-14. Epub 2014 Aug 25.
Enterohemorrhagic Escherichia coli (EHEC), a subgroup of Shiga toxin (Stx)-producing E. coli (STEC), is a leading cause of diarrhea and hemolytic-uremic syndrome (HUS) in humans. However, urinary tract infections (UTIs) caused by this microorganism but not associated with diarrhea have occasionally been reported. We geno- and phenotypically characterized three EHEC isolates obtained from the urine of hospitalized patients suffering from UTIs. These isolates carried typical EHEC virulence markers and belonged to HUS-associated E. coli (HUSEC) clones, but they lacked virulence markers typical of uropathogenic E. coli. One isolate exhibited a localized adherence (LA)-like pattern on T24 urinary bladder epithelial cells. Since the glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer) are well-known receptors for Stx but also for P fimbriae, a major virulence factor of extraintestinal pathogenic E. coli (ExPEC), the expression of Gb3Cer and Gb4Cer by T24 cells and in murine urinary bladder tissue was examined by thin-layer chromatography and mass spectrometry. We provide data indicating that Stxs released by the EHEC isolates bind to Gb3Cer and Gb4Cer isolated from T24 cells, which were susceptible to Stx. All three EHEC isolates expressed stx genes upon growth in urine. Two strains were able to cause UTI in a murine infection model and could not be outcompeted in urine in vitro by typical uropathogenic E. coli isolates. Our results indicate that despite the lack of ExPEC virulence markers, EHEC variants may exhibit in certain suitable hosts, e.g., in hospital patients, a uropathogenic potential. The contribution of EHEC virulence factors to uropathogenesis remains to be further investigated.
肠出血性大肠杆菌(EHEC)是产志贺毒素(Stx)大肠杆菌(STEC)的一个亚群,是人类腹泻和溶血尿毒综合征(HUS)的主要病因。然而,偶尔也有关于这种微生物引起的与腹泻无关的尿路感染(UTI)的报道。我们对从患有UTI的住院患者尿液中分离出的三株EHEC进行了基因和表型特征分析。这些分离株携带典型的EHEC毒力标记,属于与HUS相关的大肠杆菌(HUSEC)克隆,但缺乏尿路致病性大肠杆菌典型的毒力标记。其中一株分离株在T24膀胱上皮细胞上表现出类似局部黏附(LA)的模式。由于糖鞘脂(GSLs)球三糖神经酰胺(Gb3Cer)和球四糖神经酰胺(Gb4Cer)是Stx以及肠道外致病性大肠杆菌(ExPEC)的主要毒力因子P菌毛的已知受体,因此通过薄层色谱和质谱法检测了T24细胞和小鼠膀胱组织中Gb3Cer和Gb4Cer的表达。我们提供的数据表明,EHEC分离株释放的Stxs与从T24细胞中分离出的、对Stx敏感的Gb3Cer和Gb4Cer结合。所有三株EHEC分离株在尿液中生长时均表达stx基因。两株菌株能够在小鼠感染模型中引起UTI,并且在体外尿液中不能被典型的尿路致病性大肠杆菌分离株竞争过。我们的结果表明,尽管缺乏ExPEC毒力标记,但EHEC变体在某些合适的宿主中,例如在医院患者中,可能表现出尿路致病潜力。EHEC毒力因子对尿路发病机制的贡献仍有待进一步研究。