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

大肠杆菌是哺乳动物和鸟类肠道微生物区系中的常见成员。它也是一种肠道病原体和肠外病原体，可在家畜和人类中引起腹泻、败血症、脑膜炎和尿路感染等感染。引起腹泻或肠外感染的菌株包含不同的基因集，这是由于通过质粒连接、噬菌体和重组事件介导的水平基因转移。近年来，大肠杆菌和其他病原性肠杆菌对抗生素的耐药性也有所增加。因此，阐明大肠杆菌与动物宿主相互作用的基本方面，以更好地了解体内可能对大肠杆菌的毒力和定植期间的生存至关重要的关键机制是非常重要的。*重要的致病性大肠杆菌包括与禽类动物感染有关的致病性大肠杆菌(APEC)。亚太经合组织是全世界家禽呼吸道和系统感染的主要原因。APEC致病的确切机制尚不完全清楚。目前，生产设施中暴发疫情的治疗包括使用抗生素，这可能导致动物和人类食物链的抗药性增加，人类可能会被家禽产品的菌株定居。因此，重要的是进一步了解这些大肠杆菌菌株的致病机制和持久性，以努力确定减少或预防继续在世界范围内造成重大经济损失的此类菌株的新方法。**在过去的几年里，我们的团队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控，磷酸(Pho)调节子的重要性，以及细菌粘附素(如菌毛)对禽类和其他肠道外致病性大肠杆菌(ExPEC)毒力的影响。我的研究小组的总体研究计划是更全面地了解肠道细菌定居宿主、适应并成功度过它们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)致病性大肠杆菌中铁摄取和调节的机制；2)磷酸盐调节子对细菌粘附素(1型菌毛)的调节。我们预计，我们的研究将有助于更好地理解肠道外大肠杆菌感染牲畜和人类的能力的关键机制。确定有助于大肠杆菌存活和持久性的关键分子可能导致开发有效的疫苗或替代使用抗生素来对抗大肠杆菌和其他对农业和食品安全重要的细菌。

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.