Identification of an immunodominant drug efflux pump in Burkholderia cepacia.
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.
Wigfield
S M
SM
University of Manchester, Manchester Royal Infirmary, 2nd Floor Clinical Sciences Building, Oxford Road, Manchester M13 9WL. wigfield@icr.ac.uk
Rigg
G P
GP
Kavari
M
M
Webb
A K
AK
Matthews
R C
RC
Burnie
J P
JP
D018528:ATP-Binding Cassette Transporters / Q000032:analysis* / Q000737:chemistry / Q000502:physiology; D001426:Bacterial Proteins; D016956:Burkholderia cepacia / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D015698:Genomic Library; D006801:Humans; D015151:Immunoblotting; D008826:Microbial Sensitivity Tests
D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; C121796:bacitracin permease