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Antimicrobial Agents and Chemotherapy, October 2009, p. 4240-4246, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00242-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cotransfer of Antibiotic Resistance Genes and a hyl_Efm-Containing Virulence Plasmid in Enterococcus faecium

Cesar A. Arias,^1,2,4,* Diana Panesso,^1,2,4, Kavindra V. Singh,^1,2 Louis B. Rice,^5,6 and Barbara E. Murray^1,2,3

Department of Internal Medicine, Division of Infectious Diseases,¹ Center for the Study of Emerging and Reemerging Pathogens, Laboratory for Antimicrobial Research,² Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, Houston, Texas,³ Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogotá, Colombia,⁴ Medical and Research Services, Louis Stokes Cleveland Department of Veterans Medical Center,⁵ Department of Medicine, Case Western Reserve University, School of Medicine, Cleveland, Ohio⁶

Received 19 February 2009/ Returned for modification 3 May 2009/ Accepted 25 July 2009

The hyl_Efm gene (encoding a putative hyaluronidase) has been found almost exclusively in Enterococcus faecium clinical isolates, and recently, it was shown to be on a plasmid which increased the ability of E. faecium strains to colonize the gastrointestinal tract. In this work, the results of mating experiments between hyl_Efm-containing strains of E. faecium belonging to clonal cluster 17 and isolated in the United States and Colombia indicated that the hyl_Efm gene of these strains is also carried on large plasmids (>145 kb) which we showed transfer readily from clinical strains to E. faecium hosts. Cotransfer of resistance to vancomycin and high-level resistance (HLR) to aminoglycosides (gentamicin and streptomycin) and erythromycin was also observed. The vanA gene cluster and gentamicin resistance determinants were genetically linked to hyl_Efm, whereas erm(B) and ant(6)-I, conferring macrolide-lincosamide-streptogramin B resistance and HLR to streptomycin, respectively, were not. A hyl_Efm-positive transconjugant resulting from a mating between a well-characterized endocarditis strain [TX0016 (DO)] and a derivative of a fecal strain of E. faecium from a healthy human volunteer (TX1330RF) exhibited increased virulence in a mouse peritonitis model. These results indicate that E. faecium strains use a strategy which involves the recruitment into the same genetic unit of antibiotic resistance genes and determinants that increase the ability to produce disease. Our findings indicate that the acquisition of the hyl_Efm plasmids may explain, at least in part, the recent successful emergence of some E. faecium strains as nosocomial pathogens.

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* Corresponding author. Mailing address: 6431 Fannin St., Room 2.112 MSB, University of Texas Medical School, Houston, TX 77030. Phone: (713) 500-6738. Fax: (713) 500-5495. E-mail: caa22{at}cantab.net

Published ahead of print on 10 August 2009.

These authors contributed equally to this work.

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Antimicrobial Agents and Chemotherapy, October 2009, p. 4240-4246, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00242-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.