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Aspergillus fumigatus CYP51 sequence: potential basis for fluconazole resistance

T D Edlind1, K W Henry, K A Metera

  • 1MCP Hahnemann University, Philadelphia, Pennsylvania 19129, USA. edlind@drexel.edu

Medical Mycology
|July 12, 2001
PubMed

Insights

Aspergillus fumigatus is resistant to fluconazole due to its CYP51 gene. Comparing sequences with Candida albicans suggests a specific amino acid change, Ile301, may cause this azole antifungal resistance.

Area of Science:

  • Medical Mycology
  • Molecular Biology
  • Drug Resistance

Background:

  • Azole antifungal agents target cytochrome P450 sterol 14alpha-demethylase (CYP51).
  • Aspergillus fumigatus exhibits intrinsic resistance to fluconazole, a widely used azole.
  • Candida albicans provides a model for studying azole susceptibility and resistance mechanisms.

Purpose of the Study:

  • To investigate the molecular basis of fluconazole resistance in Aspergillus fumigatus.
  • To compare the CYP51 gene sequence of A. fumigatus with fluconazole-susceptible and resistant Candida albicans strains.
  • To identify specific amino acid residues potentially responsible for azole resistance.

Main Methods:

  • Cloning and sequencing of the Aspergillus fumigatus CYP51 gene.
  • Bioinformatic analysis and comparison of CYP51 sequences between A. fumigatus and C. albicans.
  • Hypothesis generation based on sequence homology and known resistance mutations.

Main Results:

  • The CYP51 gene from A. fumigatus was successfully cloned and sequenced.
  • Sequence comparison revealed a specific residue, Ile301 in A. fumigatus, corresponding to Thr315 in C. albicans.
  • This residue is hypothesized to play a role in substrate binding and azole resistance.

Conclusions:

  • The study provides a molecular hypothesis for fluconazole resistance in A. fumigatus.
  • The identified Ile301 residue in A. fumigatus CYP51 is a potential key factor in its intrinsic azole resistance.
  • Further studies are warranted to confirm the role of this residue in drug resistance mechanisms.

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