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Antimicrobial Agents and Chemotherapy, June 2009, p. 2283-2288, Vol. 53, No. 6
0066-4804/09/$08.00+0     doi:10.1128/AAC.00123-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Module Located at a Chromosomal Integration Hot Spot Is Responsible for the Multidrug Resistance of a Reference Strain from Escherichia coli Clonal Group A{triangledown} ,{dagger}

Mathilde Lescat,1 Alexandra Calteau,2 Claire Hoede,1 Valérie Barbe,3 Marie Touchon,4,5 Eduardo Rocha,4,5 Olivier Tenaillon,1 Claudine Médigue,2 James R. Johnson,6 and Erick Denamur1*

INSERM U722 and Université Paris 7 Denis Diderot, Site Xavier Bichat, 16 rue Henri Huchard, 75018 Paris, France,1 Commissariat à l'Energie Atomique (CEA), Direction des Sciences du Vivant, Institut de Génomique, Atelier de Génomique Comparative, CNRS UMR8030, 91057 Evry Cedex, France,2 Commissariat à l'Energie Atomique (CEA), Direction des Sciences du Vivant, Institut de Génomique, Génoscope, 91057 Evry Cedex, France,3 Institut Pasteur, Microbial Evolutionary Genomics; CNRS, URA2171, F-75015 Paris, France,4 Université Paris 6 Pierre et Marie Curie, Atelier de BioInformatique, F-75005, Paris, France,5 Mucosal and Vaccine Research Center, Veterans Affairs Medical Center, and Department of Medicine, University of Minnesota, Minneapolis, Minnesota6

Received 28 January 2009/ Returned for modification 3 March 2009/ Accepted 31 March 2009

Escherichia coli clonal group A (CGA) commonly exhibits a distinctive multidrug antimicrobial resistance phenotype—i.e., resistance to ampicillin, chloramphenicol, streptomycin, sulfonamides, tetracycline, and trimethoprim (ACSSuTTp)—and has accounted for up to 50% of trimethoprim-sulfamethoxazole-resistant E. coli urinary tract infections in some locales. Annotation of the whole-genome sequencing of UMN026, a reference CGA strain, clarified the genetic basis for this strain's ACSSuTTp antimicrobial resistance phenotype. Most of the responsible genes were clustered in a unique 23-kbp chromosomal region, designated the genomic resistance module (GRM), which occurred within a 105-kbp genomic island situated at the leuX tRNA. The GRM is characterized by numerous remnants of mobilization and rearrangement events suggesting multiple horizontal transfers. Additionally, comparative genomic analysis of the leuX tRNA genomic island in 14 sequenced E. coli genomes showed that this region is a hot spot of integration, with the presence/absence of specific subregions being uncorrelated with either the phylogenetic group or the pathotype. Our data illustrate the importance of whole-genome sequencing in the detection of genetic elements involved in antimicrobial resistance. Additionally, this is the first documentation of the blaTEM and dhfrVII genes in a chromosomal location in E. coli strains.


* Corresponding author. Mailing address: INSERM U722, Site Xavier Bichat, 16 rue Henri Huchard, 75018 Paris, France. Phone: 33157277739. Fax: 33157277724. E-mail: erick.denamur{at}inserm.fr

{triangledown} Published ahead of print on 13 April 2009.

{dagger} Supplemental material for this article may be found at http://aac.asm.org/.


Antimicrobial Agents and Chemotherapy, June 2009, p. 2283-2288, Vol. 53, No. 6
0066-4804/09/$08.00+0     doi:10.1128/AAC.00123-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.