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

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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.