Evolution of Microbial Host Specificity in E. coli

大肠杆菌是人类和动物肠道正常微生物植物群的一部分。一般认为E.大肠杆菌可以在不同的动物之间传播，因此被认为是宿主通才。然而，越来越多的文献表明，许多菌株是宿主专化者，并且这种细菌物种可能代表物种复合体（即，包括许多细菌物种）。因此，它的遗传多样性可能反映了这种微生物在各种动物和非动物宿主环境中的进化辐射。E.大肠杆菌在动物肠道中定植的能力取决于它对宿主肠道微环境生理条件的“感知和反应”能力，以及与内源性微生物菌群竞争生存和复制的能力。据推测，这种感觉基因组，或调节组，将在强大的进化选择压力下，作为一种适应性和决定性的力量，驱动主机特异性。基于我们最近的出版物（通过1年NSERC资助），我们已经确定了新的单核苷酸多态性（SNP）生物标志物的大肠杆菌。大肠杆菌中，相关的宿主特异性使用逻辑回归分析的DNA序列变异的调节[基因间区域（ITGR）]。数据支持我们的假设，即ITGR上印有宿主特定信息。这不同于传统的生物信息学方法（即，无监督学习），其通常不能解析这些复杂的宿主特异性生物标志物模式。在目前的建议中，我们打算进一步研究宿主特异性E。通过使用基因修饰方法检查宿主特异性菌株（通过ITGR生物标志物分析鉴定）在不同实验室动物（小鼠、沙鼠和仓鼠）之间交叉传播的能力，此外，我们建议使用全基因组测序（WGS）和靶向ITGR测序方法，以确定宿主特异性生物标志物在一个大的库中的E。大肠杆菌分离株从广泛的动物宿主中收集。 该研究将有助于描述E.大肠杆菌，与该物种进化辐射到不同的动物宿主，并确定在宿主选择压力下的基因组的关键区域。这些发现是非常重要的，因为它们可以用来确定紧急致病性大肠杆菌的宿主来源。可以从一种动物宿主传播到另一种动物宿主的大肠杆菌菌株（即， 产志贺毒素E. coli）。这项研究还将有助于确定可用于跟踪水/食品环境中粪便污染的宿主来源的遗传靶点-这些工具可用于环境科学家/监管机构/行业专业人员改善微生物风险评估和制定风险缓解措施以控制水/食品污染（即，水源保护）。

Escherichia coli is part of the normal microbial gut flora of humans and animals. It is generally believed that E. coli can transmit between different animals and is therefore considered a host-generalist. However, a growing body of literature demonstrates that many strains are host-specialists and that this bacterial species may represent a species-complex' (i.e., comprised of many bacterial species). Consequently, its genetic diversity may be reflective of the evolutionary radiation of this microbe into a wide variety of animal and non-animal host environments. The ability of E. coli to colonize the gut of an animal depends on its ability to 'sense-and-respond' to the physiological conditions of the host gut microenvironment and compete with endogenous microflora for survival and replication. It is hypothesized that this sensory genome, or regulome, would be under strong evolutionary selection pressure as an adaptive and deterministic force that drives host-specificity. Based on our recent publications (funded through a 1 yr NSERC), we have identified novel single nucleotide polymorphic (SNP) biomarkers of E. coli that correlate with host-specificity using logic regression analysis of DNA sequence variations in the regulome [intergenic regions (ITGRs)]. The data support our hypothesis that ITGRs are embossed with host-specific information. This is unlike traditional bioinformatic approaches (i.e., unsupervised learning) that have generally fail to resolve these complex host-specific biomarker patterns. In the current proposal we intend to further study the host-specific nature of E. coli by examining the ability of host-specific strains (identified by ITGR biomarker analysis) to cross-transmit between different laboratory animals (mice, gerbils and hamsters) using gene doctoring methods. Furthermore, we propose to use whole genome sequencing (WGS) and a targeted ITGR sequencing approach to identify host-specific biomarkers in a large library of E. coli isolates collected from a wide range of animal hosts. The research will be instrumental in characterizing population genetic structures of E. coli that are associated with the evolutionary radiation of this species into different animal hosts, and identify key areas of the genome under host-selection pressure. These findings are critically important, as they can be used to identify host-sources of emergent disease-causing E. coli strains that may transmit from one animal host into another animal host (i.e., shigatoxin producing E. coli). This research will also help identify genetic targets useful for tracking host sources of fecal pollution in water/food environments - tools that are useful for environmental scientists/regulators/industry professionals for improving microbial risk assessment and developing risk mitigation measures to control contamination of water/food (i.e., source water protection).