Kossow Annelene, Zhang Wenlan, Bielaszewska Martina, Rhode Sophie, Hansen Kevin, Fruth Angelika, Rüter Christian, Karch Helge, Mellmann Alexander
Institute of Hygiene and National Consulting Laboratory for Hemolytic Uremic Syndrome (HUS), University Hospital Muenster, Münster, Germany.
National Reference Centre for Salmonella and Other Bacterial Enterics, Robert Koch-Institute, Wernigerode, Germany.
J Clin Microbiol. 2016 May;54(5):1357-63. doi: 10.1128/JCM.02897-15. Epub 2016 Mar 16.
Alongside the well-characterized enterohemorrhagic Escherichia coli (EHEC) O157:H7, serogroup O157 comprises sorbitol-fermenting typical and atypical enteropathogenic E. coli (EPEC/aEPEC) strains that carry the intimin-encoding gene eae but not Shiga toxin-encoding genes (stx). Since little is known about these pathogens, we characterized 30 clinical isolates from patients with hemolytic uremic syndrome (HUS) or uncomplicated diarrhea with respect to their flagellin gene (fliC) type and multilocus sequence type (MLST). Moreover, we applied whole-genome sequencing (WGS) to determine the phylogenetic relationship with other eae-positive EHEC serotypes and the composition of the rfbO157 region. fliC typing resulted in five fliC types (H7, H16, H34, H39, and H45). Isolates of each fliC type shared a unique ST. In comparison to the 42 HUS-associated E. coli (HUSEC) strains, only the stx-negative isolates with fliCH7 shared their ST with EHEC O157:H7/H(-) strains. With the exception of one O157:H(-) fliCH16 isolate, HUS was exclusively associated with fliCH7. WGS corroborated the separation of the fliCH7 isolates, which were closely related to the EHEC O157:H7/H(-) isolates, and the diverse group of isolates exhibiting different fliC types, indicating independent evolution of the different serotypes. This was also supported by the heterogeneity within the rfbO157 region that exhibited extensive recombinations. The genotypic subtypes and distribution of clinical symptoms suggested that the stx-negative O157 strains with fliCH7 were originally EHEC strains that lost stx The remaining isolates form a distinct and diverse group of atypical EPEC isolates that do not possess the full spectrum of virulence genes, underlining the importance of identifying the H antigen for clinical risk assessment.
除了特征明确的肠出血性大肠杆菌(EHEC)O157:H7外,O157血清群还包括发酵山梨醇的典型和非典型肠致病性大肠杆菌(EPEC/aEPEC)菌株,这些菌株携带编码紧密黏附素的基因eae,但不携带志贺毒素编码基因(stx)。由于对这些病原体了解甚少,我们对30株来自溶血尿毒综合征(HUS)患者或无并发症腹泻患者的临床分离株进行了鞭毛蛋白基因(fliC)类型和多位点序列分型(MLST)分析。此外,我们应用全基因组测序(WGS)来确定与其他eae阳性EHEC血清型的系统发育关系以及rfbO157区域的组成。fliC分型产生了五种fliC类型(H7、H16、H34、H39和H45)。每种fliC类型的分离株共享一个独特的序列型(ST)。与42株与HUS相关的大肠杆菌(HUSEC)菌株相比,只有fliCH7的stx阴性分离株与EHEC O157:H7/H(-)菌株共享其序列型。除了一株O157:H(-)fliCH16分离株外,HUS仅与fliCH7相关。WGS证实了fliCH7分离株与EHEC O157:H7/H(-)分离株密切相关,以及表现出不同fliC类型的不同分离株群体,表明不同血清型是独立进化的。rfbO157区域内的异质性也支持了这一点,该区域表现出广泛的重组。基因型亚型和临床症状分布表明,fliCH7的stx阴性O157菌株最初是丢失了stx的EHEC菌株。其余分离株形成了一组独特且多样的非典型EPEC分离株,它们不具备完整的毒力基因谱,这突出了鉴定H抗原对临床风险评估的重要性。