Coliscope: a sequencing project for the understanding of commensalism and virulence emergence in the Escherichia coli/Shigella species
species E. coli/Shigella has both the characteristics to be
(i) composed of natural isolates with various lifestyles and (ii) a
laboratory model organism.
E. coli is an inhabitant of the gut microbiota of vertebrates, including humans, as well as a pathogen frequently involved in a broad spectrum of intestinal and extraintestinal diseases. In humans, E. coli and Shigella are responsible worldwide for some of the most common and severe infectious diseases, including diarrhoea, urinary tract infections, sepsis and neonatal meningitis (Donnenberg 2002). Furthermore, E. coli is the one of the most common etiologic agent of nosocomial infections. E. coli is also a model organism for which an extensive knowledge of its molecular biology and physiology has been accumulated.
The genetic population structure of E. coli
is globally clonal. Phylogenetic analysis has shown that the species
is composed of five main phylogenetic groups (A, B1, E, D and
B2). Pathogenic E. coli strains are derived from commensal
strains by several mechanisms, including acquisition of “virulence”
operons, inactivation of genes and allelic variations. However, the
role of the chromosomal genetic background in pathogenicity is
attested to by the observed link between the type of pathology and the
phylogenetic groups of the species (Escobar-Páramo et al.,
2004a). Thus, it is mandatory to know the commensal genomic diversity
to understand the emergence of the virulence. Up to now, genome
sequencing projects have been concentrated on pathogenic strains, with
the exception of the laboratory adapted E. coli K12 strain,
which is not representative of the species diversity. In addition, the
closest sequenced genomes available today for genomic comparison are
from the species Salmonella enterica, which has diverged 120-160
millions years ago (Ochman and Wilson, 1987). This long divergence
time renders the comparative analyses difficult to interpret.
The Genoscope will sequence the genomes of two commensal and four pathogenic human
The Genoscope will sequence the genomes of two
commensal and four pathogenic human E. coli strains spanning an
evolutionary time around 40 millions of years, as well as the one of
the type strain of the E. fergusonii species, the closest
E. coli related species. The list of the sequenced strains
with their main characteristics is given below.
Two strains of the B1phylogenetic group:
- Strain IAI 1, serogroup O8, was isolated from the faeces of a
healthy man in the 1980s in France, and is devoid of the main
extraintestinal virulence genes and avirulent in a mouse model of
extraintestinal infection (Picard et al., 1999).
- Strain 55989 is a diarrhea-associated isolate belonging to the
enteroaggregative E. coli pathotype recognized as an emerging
cause of diarrhea in children and adults worldwide (Bernier et
Two strains of the D phylogenetic group representing the two major D sub groups:
- Strain IAI 39, serotype O7:K1, was isolated from the urine of
a patient with urinary tract infection in France in the 1980s and
is virulent in a mouse model of extraintestinal infection (Picard
et al., 1999).
- Strain UMN026, serotype O17:K52:H18, is a representative of a
recently emerged E. coli clonal group (“clonal group A”) that is
now a widely disseminated cause of drug-resistant urinary tract
infections and other extraintestinal infections. It was isolated
from a woman with uncomplicated acute cystitis in Minnesota in
1999 (Manges et al., NEJM 2001) and is highly virulent in a mouse
model of extraintestinal infection.
Two strains of the B2 phylogenetic group:
- Strain ED1a, serogroup O81, was isolated from the faeces of a
healthy man who did not take antibiotics at least six months
before the sampling in the 2000s in France. This strain represents
a faeces dominant and persistent (over a six month period) clone,
is devoid of the main extraintestinal virulence genes and
avirulent in a mouse model of extraintestinal infection
(Escobar-Páramo et al., 2004b).
- Strain S88, serotype O45:K1, was isolated in 1999 from the
cerebro-spinal fluid of a late onset neonatal meningitis case in
France (Bonacorsi et al., 2003). This strain is highly virulent in
a mouse model of extraintestinal infection.
Strain ATCC 35469T, the type strain of the E. fergusonii
species. This strain is not virulent in the extra-intestinal mouse
model. E. fergusonii strains have been isolated from human and
animal, sometimes in pathogenic conditions (Farmer et al.,
The strains will be available
The strains will be available at the collection de
l’Institut Pasteur (IAI 1, IAI 39, ED1a, S88, 55989) or the ATCC (E. fergusonii, UMN026).
As the gene content is very variable among E. coli species, the newly described genes will enrich the E. coli gene pool. Taking into account the E. coli/Shigella genome projects led by other groups, the scientific community will have the unique opportunity to have 19 genomes from a single species for comparative genomics.
- Bernier, C, P. Gounon, and C. Le Bouguénec. 2002. Identification of an aggregative fimbria (AAF) type III-encoding operon in enteroaggregative Escherichia coli as a sensitive probe for detecting the AAF-encoding operon family. Infect. Immun., 70: 4302-4311.
- Bonacorsi, S. P., O. Clermont, V. Houduoin, C. Cordevant, N. Brahimi, A. Marecat, C. Tinsley, X. Nassif, M. Lange, and E. Bingen. 2003. Molecular analysis and experimental virulence of french and north american Escherichia coli neonatal meningitis isolates; Identification of new virulent clone. J Infect Dis 187:1895-906.
- Donnenberg, M. 2002. Escherichia coli virulence mechanisms of versatile pathogen. Elsevier Science Ed ed, San Diego California.
- Escobar-Páramo, P., O. Clermont, A. Blanc-Potard, H. Bui, C. Le Bouguenec, and E. Denamur. 2004a. A specific genetic background is required for acquisition and expression of virulence factors in Escherichia coli. Mol Biol Evol 21:1085-1094.
- Escobar-Páramo P., K. Grenet, A. Le Menac’h, L. Rode, E. Salgado, C. Amorin, S. Gouriou, B. Picard, M. C. Rahimy, A. Andremont, E. Denamur, and Ruimy R. 2004b. Large-scale population structure of human commensal Escherichia coli isolates. Appl Environ Microbiol, 70: 5698-5700.
- Farmer III, J. J., G. R. Fanning, B. R. Davis, C. M. O’Hara, C. Riddle, F.W. Hickman-Brenner, M. A. Asbury, V. A. Lowery III and D. J. Brenner. 1985. Escherichia fergusonii and Enterobacter taylorae, two new species of Enterobacteriaceae from clinical
specimens. J Clin Microbiol, 21:77-81.
- Manges A. R., J. R. Johnson, B. Foxman, T. T. O’Bryan, K. E. Fullerton, and L. W. Riley. 2001. Widespread distribution of urinary tract infections caused by a multidrug-resistant Escherichia coli clonal group. N Engl J Med, 345:1007-1013.
- Ochman H., and Wilson A.C. 1987. Evolution in bacteria: evidence for an universal substitution rate in cellular genomes. J Mol Evol, 26: 74-86.
- Picard, B., J. Garcia, S. Gouriou, P. Duriez, N. Brahimi, E. Bingen, J. Elion, and E. Denamur. 1999. The link between phylogeny and virulence in Escherichia coli extraintestinal infection. Infect Immun, 67:546-553.
A consortium made of :
- Erick Denamur, Olivier Tenaillon, Odile Bouvet et Olivier Clermont, INSERM U722, Paris
- Chantal Le Bouguénec, Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, Paris
- Stéphane Bonacorsi et Edouard Bingen, EA 3105 Université Paris VII, Paris
- Eduardo Pimentel Cachapuz Rocha et Antoine Danchin, URA CNRS 2171, Institut Pasteur, Paris
- Pierre Darlu, INSERM U535, Villejuif
- Ivan Matic, INSERM U571, Paris
- Jean Marc Ghigo, URA CNRS 2172, Institut Pasteur, Paris
- Xavier Nassif, INSERM U570, Paris
- Claudine Médigue, CNRS-UMR 8030, Genoscope, Evry
- James R. Johnson, Minneapolis VA Medical Center, Minneapolis,
- Dominique Schneider, CNRS UMR5163, Grenoble