背景:大肠杆菌是一种定植于各种宿主物种的机会病原体。然而,大肠杆菌的遗传谱系在多大程度上适应或限制于特定宿主,并且这种适应或限制的基因组决定簇知之甚少。
结果:我们从四个国家(德国,英国,西班牙,和越南),从五个宿主物种(人类,猪,牛,鸡肉,和野猪)超过16年,来自健康和患病的宿主,构建1198个全基因组测序的大肠杆菌分离株的集合。我们鉴定了特定大肠杆菌谱系与分离它们的宿主之间的关联。一项全基因组关联研究(GWAS)确定了几个与人类相关的大肠杆菌基因,牛,或者鸡宿主,而没有发现与猪宿主相关的基因。与人类宿主相关的9个连续基因(统称为nan-9)的计算机表征表明,这些基因参与唾液酸(Sia)的代谢。相比之下,先前描述的唾液酸调节子称为唾液酸调节子(即nanRATEK-yhcH,nanXY,和nanCMS)与任何宿主物种无关。用Δnan-9大肠杆菌突变菌株进行体外生长实验,使用唾液酸5-N-乙酰神经氨酸(Neu5Ac)和N-羟乙酰神经氨酸(Neu5Gc)作为唯一的碳源,与野生型相比,显示出受损的生长行为。
结论:这项研究提供了对可能有助于大肠杆菌宿主特异性的遗传决定子的广泛分析。我们的发现应该为(抗菌素耐药)大肠杆菌的风险分析和流行病学监测提供信息。
Escherichia coli is an opportunistic pathogen which colonizes various host species. However, to what extent genetic lineages of E. coli are adapted or restricted to specific hosts and the genomic determinants of such adaptation or restriction is poorly understood.
We randomly sampled E. coli isolates from four countries (Germany, UK, Spain, and Vietnam), obtained from five host species (human, pig, cattle, chicken, and wild boar) over 16 years, from both healthy and diseased hosts, to construct a collection of 1198 whole-genome sequenced E. coli isolates. We identified associations between specific E. coli lineages and the host from which they were isolated. A genome-wide association study (GWAS) identified several E. coli genes that were associated with human, cattle, or chicken hosts, whereas no genes associated with the pig host could be found. In silico characterization of nine contiguous genes (collectively designated as nan-9) associated with the human host indicated that these genes are involved in the metabolism of sialic acids (Sia). In contrast, the previously described sialic acid regulon known as sialoregulon (i.e. nanRATEK-yhcH, nanXY, and nanCMS) was not associated with any host species. In vitro growth experiments with a Δnan-9 E. coli mutant strain, using the sialic acids 5-N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) as sole carbon source, showed impaired growth behaviour compared to the wild-type.
This study provides an extensive analysis of genetic determinants which may contribute to host specificity in E. coli. Our findings should inform risk analysis and epidemiological monitoring of (antimicrobial resistant) E. coli.