Escherichia coli Antibiotic Resistance
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? 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.
Are there traits that promote the acquisition of virulence or antibiotic resistance? 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.
What traits distinguish a pathogenic from a commensal strain? 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.
What traits specifically adapt E. coli to human hosts? 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.
What does commensal intraclone evolution look like? 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.
Project Data for the following strains can be found by searching in NCBI
E. coli B088 E. coli B185 E. coli B354 E. coli FVEC 1302 E. coli FVEC 1412 E. coli FVEC 1465 E. coli H299 E. coli H736 E. coli M605 E. coli M718 E. coli TA143 E. coli TA206 E. coli TA271 E. coli TA280 E. coli H591 E. coli H001 E. coli E560 E. coli TA014 E. coli H223 E. coli E1002 E. coli B921 E. coli TA255 E. coli R527 E. coli M056 E. coli H617 E. coli H588 E. coli H413 E. coli E1114 E. coli TA144 E. coli B574 E. coli E267 E. coli B108 E. coli B671 E. coli H378 E. coli B367 E. coli TA447 E. coli H386 E. coli H296 E. coli H305 E. coli B175 E. coli H420 E. coli TA249 E. coli H454 E. coli T426 E. coli E704 E. coli H605 E. coli TA054 E. coli TA008 E. coli H461 E. coli H383 E. coli TA464 E. coli R424 E. coli E1167 E. coli E1520 E. coli E482 E. coli H120 E. coli H252 E. coli H263 E. coli H489 E. coli M863 E. coli TA007 E. coli TW10509 E. coli B706 E. coli E1118 E. coli E1492 E. coli H185 E. coli H218 E. coli H220 E. coli H288 E. coli H442 E. coli H504 E. coli H593 E. coli H660 E. coli M646 E. coli PUTI459 E. coli R529 E. coli T408 E. coli TA004 E. coli TA024 E. coli TA103 E. coli TA141 E. coli TA435 Escherichia sp. B646 E. albertii B090 E. albertii B156 E. fergusonii B253 E. coli B093 E. coli E101 E. coli H397 E. coli M114 v2 E. coli H494 E. coli TA124 E. coli K12 (GB) E. coli M919 (V2) E. coli H730 E. coli B799
This sequencing project was supported by the National Institute of Allergy and Infectious Disease, National Institutes of Health funded Genome Sequencing Center for Infectious Diseases at the Broad Institute.