Salicylate, Iron Starvation May Induce Antibiotic Resistance In CF Patients

NEW YORK (Reuters Health) - Antibiotic selective pressure is not required for Burkholderia cenocepacia, an important pathogen in cystic fibrosis (CF), to acquire antibiotic resistance, investigators report in the February issue of the Journal of Clinical Investigation. They found that salicylate, produced by many such isolates, and low iron concentrations, which are common in the CF lung, upregulate the antibiotic efflux pump.

B. cenocepacia, a member of the B. cepacia complex of strains, is associated with epidemic spread and increased clinical virulence, the team explains. Lead investigator Dr. Jane L. Burns, of Children's Hospital and Regional Medical Center in Seattle, and associates characterized the five open reading frames in the cluster of genes that confers resistance to antibiotics and to common disinfectants.

Antibiotic-sensitive bacteria transfected with the entire gene cluster demonstrate active efflux of chloramphenicol and salicylate, they report. Moreover, B. cenocepacia and related organisms actively secrete salicylate, an iron-chelating molecule, which they found could up-regulate the efflux pump.

"If salicylate is the natural substrate for this efflux pump and the pump is regulated by low iron concentrations, this would imply that the milieu of the CF lung would be sufficient to induce antibiotic resistance in isolates of B. cepacia complex, even without the selective pressure of antibiotics," they conclude.

Source: J Clin Invest 2004;113:464-473. [ Google search on this article ]

MeSH Headings: Biological Factors : Biological Phenomena : Biological Phenomena, Cell Phenomena, and Immunity : Biological Sciences : Biology : Drug Resistance, Microbial : Genetics : Genetics, Microbial : Immunologic and Biological Factors : Microbiologic Phenomena : Pharmacogenetics : Siderophores : Chemical Actions and Uses : Chemical Actions : Biological Sciences : Chemicals and Drugs