An invertebrate model to evaluate virulence in Aspergillus fumigatus: the role of azole resistance

Med Mycol. 2014 Apr;52(3):311-9. doi: 10.1093/mmy/myt022. Epub 2014 Feb 4.

Abstract

The impact of different mutations in the Aspergillus fumigatus ergosterol biosynthesis pathway on pathogenesis has been evaluated using a simple invertebrate mini host, the caterpillar Galleria mellonella. A set of strains that includes clinical isolates and isogenic mutants with mutations at the cyp51A gene conferring azole resistance were studied. All strains demonstrated a similar in vitro growth pattern and are equally virulent against the insect larvae. These results suggest that in A. fumigatus acquisition of this particular azole-resistance mechanism would not imply any significant change in virulence. G. mellonella may provide a convenient and inexpensive model for the in vivo prescreening of mutants of A. fumigatus, contributing to the generation of a hypotheses that can be further tested in refined experiments in mammalian models.

Keywords: cyp51A gene; isogenic mutants; nonmammalian model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology*
  • Aspergillosis / microbiology*
  • Aspergillus fumigatus / enzymology
  • Aspergillus fumigatus / growth & development
  • Aspergillus fumigatus / pathogenicity*
  • Azoles / pharmacology*
  • Cytochrome P-450 Enzyme System / genetics
  • Disease Models, Animal*
  • Drug Resistance, Fungal*
  • Fungal Proteins / genetics
  • Humans
  • Larva
  • Lepidoptera*
  • Virulence

Substances

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