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-2014-06622
• 负责人: Dozois, Charles
• 金额: $ 4.44万
• 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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=649565
• 关键词: Virulence; persistence; mechanisms; pathogenic; Escherichia

Escherichia coli is a common member of the intestinal microbiota of mammals and birds. It is also both an intestinal pathogen and an extra-intestinal pathogen that can cause infections such as diarrhea, septicemia, meningitis and urinary tract infections in domestic animals and humans. Strains causing either diarrhea or extra-intestinal infections contain distinct sets of genes due to horizontal gene transfer mediated by plasmid conjugation, bacteriophages, and recombination events. In recent years, E. coli and other pathogenic enterobacteria have also acquired increased resistance to antibiotics. As such, it is important to elucidate fundamental aspects of interactions of E. coli with animal hosts to better understand key mechanisms in vivo 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 in 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 world-wide. **Over the past several years, our group and others have investigated the importance of specific virulence factors including metal transporters and their regulation, the importance of the phosphate (Pho) regulon, and bacterial adhesins such as fimbriae for the virulence of avian and other extra-intestinal pathogenic E. coli (ExPEC). The overall research programme of my research 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) Mechanisms of iron uptake and regulation in pathogenic E. coli ; 2) Regulation of the bacterial adhesin (type 1 fimbriae) by the phosphate regulon. We anticipate our research will lead to better understanding of key mechanisms underlying the ability of extra-intestinal E. coli pathogens to infect both livestock and humans. 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常见成员。它也是一种肠道病原体和肠外病原体，可引起家畜和人类的感染，如腹泻、败血症、脑膜炎和尿路感染。 由于质粒接合、噬菌体和重组事件介导的水平基因转移，导致腹泻或肠外感染的菌株含有不同的基因组。 近年来，E.大肠杆菌和其他致病性肠杆菌对抗生素的耐药性也增加了。因此，阐明E.大肠杆菌与动物宿主，以更好地了解体内的关键机制，可能是至关重要的大肠杆菌。大肠杆菌的毒力和存活率。 * 致病性E.主要的大肠杆菌包括那些与家禽中的动物感染相关的称为禽致病性大肠杆菌的大肠杆菌。coli（APEC）。APEC是全球家禽呼吸道和全身感染的主要原因。 APEC如何导致疾病的确切机制尚未完全了解。目前，在生产设施中对疫情的治疗涉及使用抗生素，这可能导致动物和人类食物链中的耐药性增加，人类可能被来自家禽产品的菌株定殖。 因此，进一步了解这些大肠杆菌的致病机制和持久性是重要的。大肠杆菌菌株，以努力确定减少或预防这类菌株的新方法，这些菌株继续在世界范围内造成重大经济损失。** 在过去的几年里，我们的小组和其他人研究了特定毒力因子的重要性，包括金属转运蛋白及其调节，磷酸盐（Pho）调节子的重要性，以及细菌粘附素如菌毛对禽和其他肠外致病性大肠杆菌的毒力。大肠杆菌（ExPEC）。 我的研究小组的总体研究计划是更充分地了解肠细菌定植宿主，适应和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，我们希望继续开展两个主要研究领域：1）致病性大肠杆菌中铁的摄取和调节机制。2）磷酸调节子对细菌粘附素（1型菌毛）的调节。我们预计我们的研究将导致更好地了解肠外大肠杆菌能力的关键机制。大肠杆菌病原体感染牲畜和人类。鉴定了E.大肠杆菌的存活和持久性可能导致开发有效的疫苗或替代使用抗生素对抗大肠杆菌。大肠杆菌和其他对农业和食品安全有重要意义的细菌。