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Abstract：
Shiga toxin-producing Escherichia coli (STEC) infection can cause clinical manifestations ranging from diarrhea to potentially fatal hemolytic uremic syndrome (HUS). This study is aimed at identifying STEC genetic factors associated with the development of HUS in Sweden. A total of 238 STEC genomes from STEC-infected patients with and without HUS between 1994 and 2018 in Sweden were included in this study. Serotypes, Shiga toxin gene (stx) subtypes, and virulence genes were characterized in correlation to clinical symptoms (HUS and non-HUS), and pan-genome wide association study was performed. Sixty-five strains belonged to O157:H7, and 173 belonged to non-O157 serotypes. Our study revealed that strains of O157:H7 serotype especially clade 8 were most commonly found in patients with HUS in Sweden. stx2a and stx2a + stx2c subtypes were significantly associated with HUS. Other virulence factors associated with HUS mainly included intimin (eae) and its receptor (tir), adhesion factors, toxins, and secretion system proteins. Pangenome wide-association study identified numbers of accessory genes significantly overrepresented in HUS-STEC strains, including genes encoding outer membrane proteins, transcriptional regulators, phage-related proteins, and numerous genes related to hypothetical proteins. Whole-genome phylogeny and multiple correspondence analysis of pangenomes could not differentiate HUS-STEC from non-HUS-STEC strains. In O157:H7 cluster, strains from HUS patients clustered closely; however, no significant difference in virulence genes was found in O157 strains from patients with and without HUS. These results suggest that STEC strains from different phylogenetic backgrounds may independently acquire genes determining their pathogenicity and confirm that other non-bacterial factors and/or bacteria-host interaction may affect STEC pathogenesis.
摘要：
产生志贺毒素的大肠杆菌（STEC）感染可引起从腹泻到潜在致命的溶血性尿毒综合征（HUS）的临床表现。这项研究旨在确定与瑞典HUS发展相关的STEC遗传因素。这项研究共纳入了1994年至2018年间瑞典有和没有HUS的STEC感染患者的238个STEC基因组。血清型,志贺毒素基因（stx）亚型，和毒力基因的特征是与临床症状（HUS和非HUS）相关，并进行了全基因组关联研究。65株属于O157：H7，173株属于非O157血清型。我们的研究表明，在瑞典的HUS患者中最常见于O157：H7血清型菌株，尤其是进化枝8。stx2a和stx2a+stx2c亚型与HUS显著相关。与HUS相关的其他毒力因子主要包括内膜蛋白(eae)及其受体(tir),粘附因子，毒素,和分泌系统蛋白。Pangenome广泛关联研究确定了HUS-STEC菌株中辅助基因的数量显着过剩，包括编码外膜蛋白的基因，转录调节因子，噬菌体相关蛋白质，和许多与假设蛋白质相关的基因。全基因组系统发育和全基因组多重对应分析不能区分HUS-STEC和非HUS-STEC菌株。在O157:H7集群中，来自HUS患者的菌株紧密聚集；然而，在患有和不患有HUS的患者的O157菌株中，毒力基因均未发现显着差异。这些结果表明，来自不同系统发育背景的STEC菌株可能独立获得决定其致病性的基因，并证实其他非细菌因素和/或细菌-宿主相互作用可能影响STEC发病机理。
