Evolution of Microbial Host Specificity in E. coli

大肠杆菌中微生物宿主特异性的进化

• 批准号: RGPIN-2017-06185
• 负责人: Neumann, Norman
• 金额: $ 1.89万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=681485
• 关键词: Evolution; Microbial; Host; Specificity; E.

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).

大肠杆菌是人类和动物的正常微生物肠道菌群的一部分。通常认为大肠杆菌可以在不同动物之间传播，因此被认为是宿主将军。但是，越来越多的文献表明许多菌株是宿主特殊者，并且这种细菌物种可能代表一种物种复杂的'（即由许多细菌种类组成）。因此，其遗传多样性可能反映了该微生物对各种动物和非动物宿主环境的进化辐射。大肠杆菌在动物的肠道上定居的能力取决于其“感知和回答”对宿主肠道微环境的生理条件的能力，并与内源性微生物竞争以生存和复制。假设该感觉基因组或调节体将处于强大的进化选择压力下，作为驱动宿主特异性的适应性和确定性力。根据我们最近的出版物（通过1年NSERC资助），我们已经确定了大肠杆菌的新型单核苷酸多态性（SNP）生物标志物，该生物标志物使用逻辑回归分析调节组中的DNA序列变化与宿主特异性相关[基因间区域（ITGRS）]。数据支持我们的假设，即ITGRS带有特定于主机的信息。这与传统的生物信息学方法（即无监督的学习）不同，这些方法通常无法解决这些复杂的宿主特异性生物标志物模式。在当前的提案中，我们打算通过检查使用基因医生在不同实验室动物（小鼠，沙漠剂和仓鼠）之间跨越不同实验室动物（小鼠，沙漠剂和仓鼠）之间交叉跨变速器的宿主特异性菌株（通过ITGR生物标志物分析鉴定）的能力，以进一步研究大肠杆菌的宿主特异性性质。此外，我们建议使用整个基因组测序（WGS）和靶向的ITGR测序方法，以在从广泛的动物宿主中收集的大型大肠杆菌分离株中鉴定宿主特异性的生物标志物。 ***这项研究将在表征大肠杆菌的种群遗传结构中发挥作用，这些遗传结构与该物种的进化辐射到不同动物宿主，并在宿主选择压力下确定基因组的关键区域。这些发现至关重要，因为它们可用于鉴定可能从一种动物宿主传播到另一种动物宿主（即产生大肠杆菌的志毒素）的引起疾病的大肠杆菌菌株的寄主。这项研究还将有助于确定水/食品环境中粪便污染的宿主来源有用的遗传目标 - 对于环境科学家/监管机构/行业专业人员有用的工具，可用于改善微生物风险评估和制定降低风险措施以控制水/食品的污染（即，源水保护）。