Targeted gene disruption of the 14-alpha sterol demethylase (cyp51A) in Aspergillus fumigatus and its role in azole drug susceptibility

Antimicrob Agents Chemother. 2005 Jun;49(6):2536-8. doi: 10.1128/AAC.49.6.2536-2538.2005.

Abstract

The role of Aspergillus fumigatus 14alpha-sterol demethylase (Cyp51A) in azole drug susceptibility was assessed. Targeted disruption of cyp51A in azole-susceptible and -resistant strains decreased MICs from 2- to 40-fold. The cyp51A mutants were morphologically indistinguishable from the wild-type strain, retaining the ability to cause pulmonary disease in neutropenic mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology*
  • Aspergillosis / microbiology
  • Aspergillus fumigatus / drug effects*
  • Aspergillus fumigatus / enzymology*
  • Aspergillus fumigatus / genetics
  • Aspergillus fumigatus / pathogenicity
  • Azoles / pharmacology*
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Resistance, Fungal
  • Ergosterol / metabolism
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Gene Deletion*
  • Humans
  • Mice
  • Mice, Inbred ICR
  • Microbial Sensitivity Tests

Substances

  • Antifungal Agents
  • Azoles
  • Fungal Proteins
  • Cytochrome P-450 Enzyme System
  • cytochrome P-450 CYP51A, Aspergillus
  • Ergosterol