Virulence of E. coli influenced by environmental signals

环境信号影响大肠杆菌的毒力

• 批准号: RGPIN-2015-05373
• 负责人: Harel, Josée
• 金额: $ 3.28万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=613511
• 关键词: Virulence; E.; coli; influenced; environmental

Escherichia coli pathogens often cycle between host dependent and host-independent lifestyles. Thus, they must adapt to changing environments and respond to different environmental cues. To endure the frequent changes in nutrient availability, bacteria possess an arsenal of regulatory and metabolic genes allowing rapid adaptation and high flexibility.  Using a pathogenic E. coli model, we are exploring the potential cross-talk between virulence and two types of bacterial metabolic responses:   a) The animal gut environment contains a rich diversity of nutrients, coming in part from the symbiotic relationships established by the microbiota. Using functional genomics, we observed an important shift in the expression of metabolic and virulence genes in pathogenic intestinal E. coli in the presence of metabolites from the gut microbiota.  We are deciphering the mechanistic details of the regulatory systems by which signals from the intestinal microbiota environment influence E. coli virulence.   b) Bacterial pathogens, including those of humans, animals, and plants, encounter phosphate (Pi)-limiting or Pi-rich environments. The phosphate (Pi)-concentration modulates the expression of the Pho regulon, which is controlled in part by the PhoB/PhoR, a two component regulatory system (TCRS). This TCRS allows bacteria to regulate phosphate assimilation pathways accordingly. Under Pi-limiting conditions, E. coli uses the transcriptional-response regulator PhoB to translate the Pi starvation signal sensed by the bacterium into gene activation or repression. We are exploring how the Pi signal is not only employed for the maintenance of bacterial Pi homeostasis but also to regulate virulence traits, including the formation of biofilm.   This work will greatly improve our knowledge on the adaptive response of pathogenic Escherichia coli to defined environment such as the gut and Pi-depleted environments. The novelty resides in a better understanding of the links between bacterial metabolism and E. coli virulence. This is important for the development of future therapeutic and prophylactic strategies against bacterial pathogens and especially relevant in animal rearing conditions.

埃希里希氏菌 大肠杆菌通常在寄主依赖和非寄主依赖之间循环 生活方式。因此，他们必须适应不断变化的环境，并对 不同的环境线索。忍受营养的频繁变化 可获得性，细菌拥有大量的调节和代谢基因库 允许快速适应和高灵活性。正在使用一个 致病性大肠杆菌模型，我们正在探索之间潜在的串扰 毒力和两种类型的细菌代谢反应： -- a) 动物的肠道环境中含有丰富多样的营养物质， 部分来自微生物区系建立的共生关系。vbl.使用 功能基因组学，我们观察到了基因表达的重要转变 肠道代谢物存在时致病性肠道大肠杆菌的代谢和毒力基因 微生物区系。我们正在破译 监管系统的机械细节，来自 肠道微生物区系环境对E. 大肠埃希菌毒力。 -- B)细菌病原体，包括人类、动物和植物的病原体； 遇到磷(PI)限制或磷丰富的环境。这个 磷酸盐(PI)浓度调节Pho调节子的表达 在一定程度上由 由PHOB/PHOR组成的两组分调控系统(TCRS)。此TCRS允许 细菌相应地调节磷的同化途径。在等电点限制的条件下，大肠杆菌使用 转录反应调节因子PHOB翻译PI饥饿信号 被细菌感知为基因激活或抑制。我们正在探索 PI信号如何不仅用于细菌PI的维持 动态平衡也是为了调节毒力特征，包括 生物膜的形成。 -- 这项工作将极大地提高我们的 关于致病性大肠杆菌对特定环境的适应性反应的知识，如肠道和 PI枯竭的环境。新奇之处在于更好地理解 细菌代谢与E. 大肠埃希菌毒力。这对未来治疗学的发展具有重要意义。 和针对细菌病原体的预防策略，特别是 与动物饲养条件相关。