The faecal flora is a common reservoir for urinary tract infection (UTI), and Escherichia coli (E. coli) is frequently found in this reservoir without causing extraintestinal infection. We investigated these E. coli reservoirs by whole-genome sequencing a large collection of E. coli from healthy controls (faecal), who had never previously had UTI, and from UTI patients (faecal and urinary) sampled from the same geographical area. We compared MLST types, phylogenetic relationship, accessory genome content and FimH type between patient and control faecal isolates as well as between UTI and faecal-only isolates, respectively. Comparison of the accessory genome of UTI isolates to faecal isolates revealed 35 gene families which were significantly more prevalent in the UTI isolates compared to the faecal isolates, although none of these were unique to one of the two groups. Of these 35, 22 belonged to a genomic island and three putatively belonged to a type VI secretion system (T6SS). MLST types and SNP phylogeny indicated no clustering of the UTI or faecal E. coli from patients distinct from the control faecal isolates, although there was an overrepresentation of UTI isolates belonging to clonal lineages CC73 and CC12. One combination of mutations in FimH, N70S/S78N, was significantly associated to UTI, while phylogenetic analysis of FimH and fimH identified no signs of distinct adaptation of UTI isolates compared to faecal-only isolates not causing UTI. In summary, the results showed that (i) healthy women who had never previously had UTI carried faecal E. coli which were overall closely related to UTI and faecal isolates from UTI patients; (ii) UTI isolates do not cluster separately from faecal-only isolates based on SNP analysis; and (iii) 22 gene families of a genomic island, putative T6SS proteins as well as specific metabolism and virulence associated proteins were significantly more common in UTI isolates compared to faecal-only isolates and (iv) evolution of fimH for these isolates was not linked to the clinical source of the isolates, apart from the mutation combination N70S/S78N, which was correlated to UTI isolates of phylogroup B2. Combined, these findings illustrate that faecal and UTI isolates, as well as faecal-only and faecal-UTI isolates, are closely related and can only be distinguished, if at all, by their accessory genome.

中文翻译：

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泌尿道致病性大肠杆菌和UTI患者及健康对照的粪便分离株的全基因组比较。

粪便菌群是尿路感染（UTI）的常见储水库，在该储水库中经常发现大肠杆菌（E. coli），而不会引起肠外感染。我们通过全基因组测序对这些大肠杆菌库进行了调查，这些测序来自健康对照（粪便）（以前从未接受过UTI）以及来自同一地区的UTI患者（粪便和泌尿）中的大量大肠杆菌。我们分别比较了患者和对照粪便分离株之间以及UTI和仅粪便分离株之间的MLST类型，系统发育关系，辅助基因组含量和FimH类型。将UTI分离株的辅助基因组与粪便分离株进行比较，发现35个基因家族与粪便分离株相比，在UTI分离株中的流行程度更高，尽管这些都不是两组中唯一的。在这35个中，有22个属于基因岛，而三个则属于VI型分泌系统（T6SS）。MLST类型和SNP系统发育史表明，与对照粪便分离株不同的患者，UTI或粪便大肠杆菌无聚集现象，尽管属于克隆谱系CC73和CC12的UTI分离株过多。FimH中的一种突变组合N70S / S78N与UTI显着相关，而对FimH和fimH的系统发育分析表明，与不引起UTI的仅粪便分离株相比，没有UTI分离株适应性明显的迹象。总而言之，结果表明：（i）以前从未接受过UTI的健康女性携带的粪便大肠杆菌与UTI和来自UTI患者的粪便分离株总体上密切相关；（ii）根据SNP分析，UTI分离株不会与仅粪便分离株分开聚类；（iii）与单纯粪便分离株相比，UTI分离株中基因岛的22个基因家族，推定的T6SS蛋白以及特定的代谢和毒力相关蛋白明显更为常见，并且（iv）这些分离株的fimH进化没有关联除突变组合N70S / S78N外，与分离株的临床来源有关，突变组合N70S / S78N与系统群B2的UTI分离株有关。综合起来，这些发现说明粪便和UTI分离株，以及仅粪便和UTI分离株密切相关，并且只能通过其辅助基因组加以区分。与仅粪便的分离株相比，UTI分离株的推定的T6SS蛋白以及与特异性代谢和毒力相关的蛋白更为常见，并且（iv）除突变以外，这些分离株的fimH的进化与分离株的临床来源无关。 N70S / S78N的组合，它与B2群的UTI分离株有关。综合起来，这些发现说明粪便和UTI分离株，以及仅粪便和UTI分离株密切相关，并且只能通过其辅助基因组加以区分。与仅粪便的分离株相比，UTI分离株的推定的T6SS蛋白以及与特异性代谢和毒力相关的蛋白更为常见，并且（iv）除突变以外，这些分离株的fimH的进化与分离株的临床来源无关。 N70S / S78N的组合，它与B2群的UTI分离株有关。综合起来，这些发现说明粪便和UTI分离株，以及仅粪便和UTI分离株密切相关，并且只能通过其辅助基因组加以区分。除了突变组合N70S / S78N以外，它与系统群B2的UTI分离株有关。综合起来，这些发现说明粪便和UTI分离株，以及仅粪便和UTI分离株密切相关，并且只能通过其辅助基因组加以区分。除了突变组合N70S / S78N以外，它与系统群B2的UTI分离株有关。综合起来，这些发现说明粪便和UTI分离株，以及仅粪便和UTI分离株密切相关，并且只能通过其辅助基因组加以区分。