Evolution of Microbial Host Specificity in E. coli

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Escherichia coli is part of the normal microbial gut flora of humans and animals. It is generally believed that E. coli can transmit between different animals and is therefore considered a host-generalist. However, a growing body of literature demonstrates that many strains are host-specialists and that this bacterial species may represent a ‘species-complex' (i.e., comprised of many bacterial species). Consequently, its genetic diversity may be reflective of the evolutionary radiation of this microbe into a wide variety of animal and non-animal host environments. The ability of E. coli to colonize the gut of an animal depends on its ability to 'sense-and-respond' to the physiological conditions of the host gut microenvironment and compete with endogenous microflora for survival and replication. It is hypothesized that this sensory genome, or regulome, would be under strong evolutionary selection pressure as an adaptive and deterministic force that drives host-specificity. Based on our recent publications (funded through a 1 yr NSERC), we have identified novel single nucleotide polymorphic (SNP) biomarkers of E. coli that correlate with host-specificity using logic regression analysis of DNA sequence variations in the regulome [intergenic regions (ITGRs)]. The data support our hypothesis that ITGRs are embossed with host-specific information. This is unlike traditional bioinformatic approaches (i.e., unsupervised learning) that have generally fail to resolve these complex host-specific biomarker patterns. In the current proposal we intend to further study the host-specific nature of E. coli by examining the ability of host-specific strains (identified by ITGR biomarker analysis) to cross-transmit between different laboratory animals (mice, gerbils and hamsters) using gene doctoring methods. Furthermore, we propose to use whole genome sequencing (WGS) and a targeted ITGR sequencing approach to identify host-specific biomarkers in a large library of E. coli isolates collected from a wide range of animal hosts. *** The research will be instrumental in characterizing population genetic structures of E. coli that are associated with the evolutionary radiation of this species into different animal hosts, and identify key areas of the genome under host-selection pressure. These findings are critically important, as they can be used to identify host-sources of emergent disease-causing E. coli strains that may transmit from one animal host into another animal host (i.e., shigatoxin producing E. coli). This research will also help identify genetic targets useful for tracking host sources of fecal pollution in water/food environments - tools that are useful for environmental scientists/regulators/industry professionals for improving microbial risk assessment and developing risk mitigation measures to control contamination of water/food (i.e., source water protection).