title: Salicylate induces an antibiotic efflux pump in Burkholderia cepacia complex genomovar III (B. cenocepacia).
abstract: An antibiotic efflux gene cluster that confers resistance to chloramphenicol, trimethoprim, and ciprofloxacin has been identified in Burkholderia cenocepacia (genomovar III), an important cystic fibrosis pathogen. Five open reading frames have been identified in the cluster. There is apparently a single transcriptional unit, with llpE encoding a lipase-like protein, ceoA encoding a putative periplasmic linker protein, ceoB encoding a putative cytoplasmic membrane protein, and opcM encoding a previously described outer membrane protein. A putative LysR-type transcriptional regulatory gene, ceoR, is divergently transcribed upstream of the structural gene cluster. Experiments using radiolabeled chloramphenicol and salicylate demonstrated active efflux of both compounds in the presence of the gene cluster. Salicylate is an important siderophore produced by B. cepacia complex isolates, and both extrinsic salicylate and iron starvation appear to upregulate ceoR promoter activity, as does chloramphenicol. These results suggest that salicylate is a natural substrate for the efflux pump in B. cenocepacia and imply that the environment of low iron concentration in the cystic fibrosis lung can induce efflux-mediated resistance, even in the absence of antibiotic selective pressure.
authors.affiliation: Division of Infectious Disease, Children's Hospital and Regional Medical Center, Seattle, Washington 98105, USA.
authors.forename: Bindu M
authors.initials: BM
authors.lastname: Nair
authors.forename: K-John
authors.initials: KJ
authors.lastname: Cheung
authors.forename: Adam
authors.initials: A
authors.lastname: Griffith
authors.forename: Jane L
authors.initials: JL
authors.lastname: Burns
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D042602:Burkholderia cepacia complex / Q000235:genetics / Q000378:metabolism*; D002701:Chloramphenicol / Q000378:metabolism; D002939:Ciprofloxacin / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D005810:Multigene Family; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012459:Salicylates / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D014295:Trimethoprim / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D012459:Salicylates; C074517:opc protein, bacteria; D002939:Ciprofloxacin; D002701:Chloramphenicol; D014295:Trimethoprim