Escherichia coli Antibiotic Resistance Database
Escherichia coli accounts for 17.3% of clinical infections requiring hospitalization and is the second most common source of infection behind Staphylococcus aureus (18.8%). Among outpatient infections, E. coli is the most common organism (38.6%). Currently, we are witnessing the disturbing emergence of new pathogenic E. coli strains, such as diarrheagenic O157:H7, and an increase in urinary tract pathogens. In the U.S., E. coli related urinary tract infections kill ~7200 persons annually, and the annual mortality associated with E. coli bacteremia in the U.S. is around 36,000-40,000 (Russo & Johnson, 2003); globally, ~1 million people die from diarrheagenic E. coli infections, mostly children and immunocompromised individuals. In contrast, most E. coli isolated from the gut exist as commensals and are an essential component of the flora of a healthy human and, indeed, of most animals. This ubiquitous commensal population, however, constitutes an enormous reservoir from which pathogenic strains continually emerge. The ability for E. coli to exist as a human-adapted commensal compounded with its natural tendency for frequent genetic exchange, its ubiquitous presence, and the enormous, diverse, and largely uncharacterized reservoir of genetic variation found within the species' collective genomes all contribute to the emergence of new pathogenic strains. By significantly expanding comparative genomics to a population scale we will peer into the E. coli population, with previously unattainable resolution, and identify the genetic pathways leading to the emergence of human-adapted, pathogenic strains.
This project has five main foci:
- What is the genetic diversity within E. coli and how is it generated?
- Are there traits that promote the acquisition of virulence or antibiotic resistance?
- What traits distinguish a pathogenic from a commensal strain?
- What traits specifically adapt E. coli to human hosts?
- What does commensal intraclone evolution look like?
We propose to sequence E. coli genomes representing all four phylogenetic sub?species groups and to encompass numerous commensal and pathogenic isolates, as well as rarely characterized environmental isolates. This broad genomic survey will define the genetic diversity within E. coli. We will characterize the diversity both in terms of nucleotide variation and the variability of loci. By comparing differences between phylogenetic sub-species groups we will be able to reconstruct the evolutionary 'history' of E. coli in terms of both the core genome and the pan-genome and identify the types of variation driving evolution of human adapted and pathogenic strains. We will be able to determine if there are groups that are more likely to evolve pathogenic traits or serve as genetic reservoirs for such traits.
One of the key components in the evolution of virulence and antibiotic resistance is the acquisition of mobile genetic elements, such as conjugative transposons, integrons, and plasmids. Certain plasmid incompatibility groups and integron classes are associated with particular lineages, but the molecular mechanisms are unknown. A phylogenetically coherent sampling of E. coli genomes will allow us to determine the phylogenetic components of virulence and resistance and the associated mechanisms promoting exchange of genetic elements.
This large collection of commensal E. coli can be compared to pathogenic E. coli genomes to identify those genetic features that are correlated with pathogenesis.
The collection we have compiled includes environmental, non-human commensal, and human commensal isolates. In our selection of human commensals we have emphasized a sub-species group that is particularly interesting because it is also the primary group involved with urinary tract infections in the developed world. We will ascertain if there are certain common features that predict the emergence of human-adapted strains.
We have chosen multiple isolates from three common MLST clones, ST10, ST69, and ST95, in order to determine if human commensals share common traits and if there are certain common features that predict the emergence of human-adapted strains. Strains within these clones are less than 0.02% sequence divergent, according to MLST data, although we have selected strains that differ based on plasmid content, antibiotic resistance, and possession of virulence factors. We have emphasized one clone, ST69, that is particularly interesting because it is also the primary agent of urinary tract infections in the developed world.
Photo Captions and Credits
The images on the home page are, from left to right:
- 1: Transmission electron micrograph of E. coli O157:H7 showing flagella. Pseudoreplica technique.
Source: CDC/ Peggy S. Hayes. Photo: Elizabeth H. White, M.S., 1995.
- 2 and 5: Scanning electron micrograph of Escherichia coli, grown in culture and adhered to a cover slip.
Photo: Rocky Mountain Laboratories, NIAID, NIH
- 3 and 4: Low-temperature electron micrograph of a cluster of E. coli bacteria, magnified 10,000 times. Each individual bacterium is oblong shaped.
Photo by Eric Erbe, digital colorization by Christopher Pooley, both of USDA, ARS, EMU.