Virulence and persistence mechanisms of pathogenic Escherichia coli causing extra-intestinal infections in poultry and other animals

引起家禽和其他动物肠外感染的致病性大肠杆菌的毒力和持久性机制

• 批准号: RGPIN-2019-06642
• 负责人: Dozois, Charles
• 金额: $ 3.64万
• 依托单位: Institut national de la recherche scientifique
• 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=690224
• 关键词: Virulence; persistence; mechanisms; pathogenic; Escherichia

***Escherichia coli is a commensal of the intestinal microbiota of mammals and birds. It is also both an intestinal and an extra-intestinal pathogen that can cause infections in domestic animals and humans that are a major economic burden to agriculture and food safety. E. coli is a multi-faceted bacterium and has acquired different sets of distinct genes by horizontal gene transfer. As such, understanding its capacity to colonize animals and persist in different hosts is a challenge. It is important to elucidate fundamental aspects of interactions of E. coli with animal hosts and cells to better understand key mechanisms that may be critical for E. coli virulence and survival during colonization. ******Pathogenic E. coli of major importance include those associated with animal infections in poultry called avian pathogenic E. coli (APEC). APEC are the predominant cause of respiratory and systemic infections in poultry worldwide. The precise mechanisms of how APEC cause disease are not fully understood. Currently, treatment of outbreaks in production facilities involves use of antibiotics, which can lead to increased resistance both in animals and through the food chain to humans who can become colonized with strains from poultry products. It is therefore important to further understand pathogenic mechanisms and persistence of these E. coli strains in an effort to determine novel means of reducing or preventing such strains that continue to cause major economic losses to agriculture/food production worldwide. ******Over the past several years, our group and others have investigated the importance of specific virulence factors including metal transporters and their regulation, iron homeostasis, and the importance of the phosphate (Pho) regulon, and bacterial adhesins , such as fimbriae and autotransporter proteins, for the virulence of avian and other extra-intestinal pathogenic E. coli (ExPEC). ******The overall research program of my group is to more fully understand molecular mechanisms underlying the ability of enterobacteria to colonize the host, adapt, and successfully survive different stresses they may encounter. ******Over the course of the next grant period we wish to pursue two main research areas : 1) Regulation of the bacterial adhesin (type 1 fimbriae) by the phosphate (Pho) regulon and other regulators. 2) Characterization of novel virulence factors we have identified in avian pathogenic E. coli, which include newly identified adhesins (fimbriae and autotransporters) and toxins. ******We anticipate that our research will lead to fundamental discoveries in regulation of virulence factor expression and a better understanding of key mechanisms by which extra-intestinal E. coli infect poultry and other animals. Identifying key molecules contributing to E. coli survival and persistence may lead to the development of effective vaccines or alternatives to the use of antibiotics against E. coli and other bacteria of importance to agriculture and food safety.

***大肠杆菌是哺乳动物和鸟类肠道微生物群的共生菌。它也是一种肠道和肠道外病原体，可在家畜和人类中引起感染，对农业和食品安全造成重大经济负担。大肠杆菌是一种多面性的细菌，通过水平基因转移获得了不同的基因集。因此，了解它在动物身上定居并在不同宿主体内存活的能力是一个挑战。阐明大肠杆菌与动物宿主和细胞相互作用的基本方面对于更好地理解可能对大肠杆菌定殖期间的毒力和存活至关重要的关键机制是很重要的。******重要的致病性大肠杆菌包括那些与家禽动物感染有关的称为禽致病性大肠杆菌（APEC）的大肠杆菌。亚太经合组织是全球家禽呼吸道和全身感染的主要原因。APEC致病的确切机制尚不完全清楚。目前，在生产设施中治疗疫情涉及使用抗生素，这可能导致动物和通过食物链对人类的耐药性增强，而人类可能被家禽产品的菌株定殖。因此，有必要进一步了解这些大肠杆菌菌株的致病机制和持久性，以确定减少或预防此类菌株的新方法，这些菌株继续给全球农业/粮食生产造成重大经济损失。******在过去的几年中，我们的团队和其他人已经研究了特定毒力因子的重要性，包括金属转运蛋白及其调控，铁稳态，磷酸盐（Pho）调控的重要性，以及细菌粘附素，如菌毛和自转运蛋白，对禽和其他肠外致病性大肠杆菌（ExPEC）的毒力。******我小组的总体研究计划是更全面地了解肠杆菌定植宿主、适应并成功生存可能遇到的不同压力的能力的分子机制。******在下一个资助期内，我们希望进行两个主要研究领域：1)磷酸盐（Pho）调控和其他调控对细菌粘附素（1型菌毛）的调控。2)禽致病性大肠杆菌新毒力因子的鉴定，包括新发现的粘附素（菌毛和自转运蛋白）和毒素。******我们预计我们的研究将导致毒力因子表达调控的根本性发现，并更好地了解肠外大肠杆菌感染家禽和其他动物的关键机制。确定有助于大肠杆菌存活和持续存在的关键分子可能导致开发有效的疫苗或抗生素替代品，以对抗大肠杆菌和对农业和食品安全具有重要意义的其他细菌。