Microbial Adaptation and Evolution Towards Host Specificity

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The bacterium, Escherichia coli, is part of the normal microbial flora found in the intestines of a variety of animals and the environment. Certain strains are known to cause disease in both animals and humans. It is generally believed that E. coli can transmit between different animals and is therefore considered to be a host-generalist. However, an increasing body of literature demonstrates that strains of this bacterium are very different at the genetic level, suggesting that some strains may be better adapted to survive within certain animal hosts or environments and, consequently, may have limited ability to cross into different animal populations (i.e., they may be host-specific). Recent research in my laboratory supports this concept. The research presented in this proposal attempts to identify novel genetic biomarkers of E. coli that define which animal host(s) or environments the organism may be capable of colonizing. The research is based on the hypothesis that E. coli’s survival within the gut of a particular animal host or environment will depend on its ability to sense and respond to the physiological gut conditions of that host or environment (i.e., water or wastewater), and consequently, whether it can outcompete other microbes for the limited nutrients/replication sites within the niche. Since gut and environmental conditions vary widely from host-to-host and from environment-to-environment, I believe that microbial evolution will drive survival strategies towards host specialization. The ability of the bacteria to ‘sense-and-respond’ to environmental conditions in the gut/environment is largely encoded in the ‘sensory genome’ (i.e., transcriptome) and consequently an analysis of DNA sequences in these control regions may reveal DNA biomarker patterns that correlate with host-specificity. As a corollary hypothesis I believe that intergenic DNA sequences from E. coli in humans, animals and the environment are 'imprinted' with host specific information, useful for identifying the source of emergent pathogenic strains of E. coli in food and water. To accomplish this, my laboratory will: a) mass sequence targeted areas of the genome (already shown by our group to carry host-specific biomarkers) across 5000 animal E. coli isolates, and b) use whole genome sequencing of representative animal isolates (supplemented with publically available genome data for human and animal isolates) to identify host-specific biomarkers using novel logic regression statistical tools developed by team members. The research is important in identifying disease-causing strains that have the potential to emerge from one animal host into another, or in the case of situations where zoonoses emerge (i.e., E. coli O104 in Europe), what animal reservoirs may have been associated with emergence. The data may also allow for development of control measures related to contamination of food and/or water.