Deep characterization of Escherichia coli in a cohort of mothers and their infants

Abstract

This work is a deep characterization of Escherichia coli (E.coli) colonization of a cohort of infants and their mothers in Trondheim, Norway. E.coli cause ~2 million deaths due to infant diarrhea and ~150 million cases of uncomplicated cystitis. However, even given this potentially severe impact on human health, almost every one of us carries about a billion E.coli cells with no problems. Furthermore, there is often almost little or no difference between a disease causing strain and one that lives commensally with the host. Our parent study examined the impact of whole gut microbial colonization on the development of atopic disease and found that early E.coli colonization of the infant was linked to protection from atopy and that the mother was found to be a likely source of infant colonization. In this thesis we first developed a simple and novel technique that allowed us to uncover limits on the diversity of colonizing E.coli strains and confirmed evidence of transmission from the mothers to the infants. We then placed these colonizing strains into a phylogenetic context and thus into the overall diversity of E. coli. This allowed us to understand and compare strains colonizing infants in a defined geographic area with the wider population structure of this species. We then investigated differences in growth characteristics of isolated E. coli strains from this cohort that were either early or late colonizers of the infant gut. In vitro competition studies revealed potential mechanisms that modulate strain competitive dynamics. Finally, through genome sequencing, we compared several phenotypic characteristics using differential gene content in order to determine enrichment profiles that may explain these traits. Enrichment comparisons included: phylogenetic, pathogenic vs. commensal, growth rate, and early or late colonization. The signatures we found can be used for further investigations into genotype-phenotype connections within E. coli strain ecology.