Azole Resistance in Aspergillus Fumigatus: A Side-Effect of Environmental Fungicide Use?

Lancet Infect Dis. 2009 Dec;9(12):789-95. doi: 10.1016/S1473-3099(09)70265-8.

Abstract

Invasive aspergillosis due to multi-azole-resistant Aspergillus fumigatus has emerged in the Netherlands since 1999, with 6.0-12.8% of patients harbouring resistant isolates. The presence of a single resistance mechanism (denoted by TR/L98H), which consists of a substitution at codon 98 of cyp51A and a 34-bp tandem repeat in the gene-promoter region, was found in over 90% of clinical A fumigatus isolates. This is consistent with a route of resistance development through exposure to azole compounds in the environment. Indeed, TR/L98H A fumigatus isolates were cultured from soil and compost, were shown to be cross-resistant to azole fungicides, and genetically related to clinical resistant isolates. Azoles are abundantly used in the environment and the presence of A fumigatus resistant to medical triazoles is a major challenge because of the possibility of worldwide spread of resistant isolates. Reports of TR/L98H in other European countries indicate that resistance might already be spreading.

MeSH terms

  • Antifungal Agents / metabolism*
  • Aspergillosis / drug therapy*
  • Aspergillus fumigatus / genetics*
  • Aspergillus fumigatus / metabolism
  • Cytochrome P-450 Enzyme System / genetics
  • Drug Resistance, Multiple, Fungal / genetics*
  • Europe
  • Fungal Proteins / genetics
  • Fungicides, Industrial / adverse effects*
  • Humans
  • Microbial Sensitivity Tests
  • Mutation
  • Soil Microbiology
  • Triazoles / metabolism*

Substances

  • Antifungal Agents
  • Fungal Proteins
  • Fungicides, Industrial
  • Triazoles
  • Cytochrome P-450 Enzyme System
  • cytochrome P-450 CYP51A, Aspergillus