Salicylate Induces an Antibiotic Efflux Pump in Burkholderia Cepacia Complex Genomovar III (B. Cenocepacia)

J Clin Invest. 2004 Feb;113(3):464-73. doi: 10.1172/JCI19710.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism
  • Burkholderia cepacia complex / genetics
  • Burkholderia cepacia complex / metabolism*
  • Chloramphenicol / metabolism
  • Ciprofloxacin / metabolism
  • Drug Resistance, Bacterial / genetics
  • Drug Resistance, Bacterial / physiology*
  • Gene Expression Profiling
  • Humans
  • Infant
  • Multigene Family
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salicylates / metabolism*
  • Sequence Analysis, DNA
  • Trimethoprim / metabolism

Substances

  • Bacterial Outer Membrane Proteins
  • Salicylates
  • opc protein, bacteria
  • Ciprofloxacin
  • Chloramphenicol
  • Trimethoprim