Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in an itraconazole resistant clinical isolate

Fungal Genet Biol. 2002 Aug;36(3):199-206. doi: 10.1016/s1087-1845(02)00016-6.


Aspergillus fumigatus is the most frequent causative agent of invasive aspergillosis. Itraconazole became available in 1990 to treat invasive aspergillosis, but instances of resistance have now been described. Drug efflux was a proposed mechanism in one itraconazole resistant clinical isolate (AF72) which accumulates low levels of the drug. Drug efflux in fungi can be mediated by ATP-binding cassette transporter (ABCT) genes, such as CDR1 in Candida albicans. Using a probe derived from CDR1, a gene, atrF, was cloned from A. fumigatus. The atrF gene product (AtrF) is 1547 amino acids long and has characteristic multidrug resistance motifs. Dot blot analysis revealed that AF72 has approximately 5-fold higher levels of atrF mRNA than susceptible isolates AF10 and H06-03 in cultures with sub-minimum inhibitory concentration (sub-MIC) levels of itraconazole. atrF is the first ABCT gene cloned from A. fumigatus, whose overexpression is correlated with itraconazole resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / chemistry
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Amino Acid Sequence
  • Antifungal Agents / pharmacology
  • Aspergillus fumigatus / drug effects
  • Aspergillus fumigatus / genetics*
  • Aspergillus fumigatus / metabolism
  • Base Sequence
  • Cloning, Molecular
  • Drug Resistance, Microbial / physiology*
  • Gene Expression Regulation, Fungal / drug effects
  • Immunoblotting
  • Itraconazole / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Sequence Data


  • ATP-Binding Cassette Transporters
  • Antifungal Agents
  • Itraconazole