Bacterial Iron Acquisition Strategies of Gram-Negative Bacteria from the Pasteurellaceae that Inhabit the Upper Respiratory Tract of Food Production Animals

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My research program involves characterizing iron acquisition systems in important Gram-negative bacterial pathogens of food production animals and developing vaccines for disease prevention. This NSERC application is focused on the pathogens responsible for bovine respiratory disease (BRD) in beef and dairy cattle. The important BRD pathogens (Mannhemia haemolytica, Histophilus somni, Pastuerella multocida) possess surface receptors to extract iron from host transferrin at the bacterial cell surface, providing the ability to proliferate independently from other microbes on the mucosal surface and cause invasive infection. Our vaccine strategy targeting these receptor proteins is based on the premise that we will eliminate the ability of BRD pathogens to proliferate and cause invasive infection but not eliminate related commensal species. However, our current understanding of the prevalence, diversity and exchange of iron acquisition genes amongst the BRD pathogens and related commensal strains is currently inadequate to gauge the reservoir of antigenic variants and the consequence of vaccination on the upper respiratory tract microbiome. Thus the main goals of this program are to determine, (i) the prevalence of iron acquisition genes, (ii) the efficiency of genetic exchange, and (ii) the functional iron acquisition capabilities of pathogenic and commensal strains and species of the Pasteurellacea family that inhabit the bovine upper respiratory tract. We will perform a comprehensive analysis of the presence and diversity of iron acquisition genes present in microbiome samples, in bacteria isolated from microbiome samples and in collections of BRD isolates. In order to evaluate the extent of genetic exchange amongst these related bacterial species we will determine whether the natural transformation systems of the BRD pathogens are functional and then test the efficiency of exchange amongst the BRD pathogens and related commensal bacteria. The ability of the bacteria to use siderophores produced by microbiome constituents or various host iron sources to support growth under iron-limited conditions will be evaluated. Knockouts of the genes will be performed to confirm their role in iron acquisition from different iron sources. This program will provide the foundation for development of rational vaccine strategy and determine what will be required for development of a single vaccine targeting all three BRD pathogens.