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Journal of Antimicrobial Chemotherapy (2002) 49, 619-624
© 2002 The British Society for Antimicrobial Chemotherapy

Identification of an immunodominant drug efflux pump in Burkholderia cepacia

S. M. Wigfielda,*, G. P. Rigga,b, M. Kavaria, A. K. Webbc, R. C. Matthewsa,b and J. P. Burniea,b

a University of Manchester and b NeuTec Pharma plc, Manchester Royal Infirmary, 2nd Floor Clinical Sciences Building, Oxford Road, Manchester M13 9WL; c Bradbury Cystic Fibrosis Unit, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LT, UK

Burkholderia cepacia, a major pathogen amongst individuals with cystic fibrosis (CF), is intrinsically resistant to most clinically available antibiotics. We report the identification of an immunodominant antigen in CF patients infected with B. cepacia, a multidrug-resistance efflux pump called BcrA. The bcrA gene encodes a 46 kDa peptide with 14 potential {alpha}-helices that belongs to the major facilitator superfamily of drug transporters. A recombinant Escherichia coli strain was constructed containing the bcrA gene, which resulted in a four-fold increase in resistance to tetracycline and an eight-fold increase in resistance to nalidixic acid. These results demonstrate that the bcrA gene is part of a drug efflux system that is potentially a major contributor to the high-level antibiotic resistance observed in B. cepacia and thus a potential target for novel therapeutics.

* Correspondence address: Institute for Cancer Research, 237 Fulham Road, London SW3 6JB, UK. Tel: +44-207-970-6113; Fax: +44-207-352-3299; E-mail: wigfield{at}icr.ac.uk


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