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Antimicrobial Agents and Chemotherapy, September 2007, p. 3247-3253, Vol. 51, No. 9
0066-4804/07/$08.00+0     doi:10.1128/AAC.00072-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Cloning, Nucleotide Sequencing, and Analysis of the AcrAB-TolC Efflux Pump of Enterobacter cloacae and Determination of Its Involvement in Antibiotic Resistance in a Clinical Isolate

Servicio Microbiología-Unidad de Investigación, Complejo Hospitalario Universitario Juan Canalejo, La Coruña, Spain,¹ Laboratorio de Microbiología, Hospital Comarcal de Valdeorras, Ourense, Spain,² Laboratory of Microbial Biofilms, Instituto de Agrobiotecnología, and Dpto. de Producción Agraria, Universidad Pública de Navarra-CSIC. Pamplona, Spain,³ Laboratorio de Microbiología, Hospital Meixoeiro, Vigo, Spain⁴

Received 17 January 2007/ Returned for modification 18 February 2007/ Accepted 5 July 2007

Enterobacter cloacae is an emerging clinical pathogen that may be responsible for nosocomial infections. Management of these infections is often difficult, owing to the high frequency of strains that are resistant to disinfectants and antimicrobial agents in the clinical setting. Multidrug efflux pumps, especially those belonging to the resistance-nodulation-division family, play a major role as a mechanism of antimicrobial resistance in gram-negative pathogens. In the present study, we cloned and sequenced the genes encoding an AcrAcB-TolC-like efflux pump from an E. cloacae clinical isolate (isolate EcDC64) showing a broad antibiotic resistance profile. Sequence analysis showed that the acrR, acrA, acrB, and tolC genes encode proteins that display 79.8%, 84%, 88%, and 82% amino acid identities with the respective homologues of Enterobacter aerogenes and are arranged in a similar pattern. Deletion of the acrA gene to yield an AcrA-deficient EcDC64 mutant (EcacrA) showed the involvement of AcrAB-TolC in multidrug resistance in E. cloacae. However, experiments with an efflux pump inhibitor suggested that additional efflux systems also play a role in antibiotic resistance. Investigation of several unrelated isolates of E. cloacae by PCR analysis revealed that the AcrAB system is apparently ubiquitous in this species.

Published ahead of print on 16 July 2007.