title: An invertebrate model to evaluate virulence in Aspergillus fumigatus: the role of azole resistance.
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.
authors.affiliation: Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Gomez-Lopez
authors.forename: A
authors.initials: A
authors.lastname: Forastiero
authors.forename: E
authors.initials: E
authors.lastname: Cendejas-Bueno
authors.forename: L
authors.initials: L
authors.lastname: Gregson
authors.forename: E
authors.initials: E
authors.lastname: Mellado
authors.forename: S J
authors.initials: SJ
authors.lastname: Howard
authors.forename: J L
authors.initials: JL
authors.lastname: Livermore
authors.forename: W W
authors.initials: WW
authors.lastname: Hope
authors.forename: M
authors.initials: M
authors.lastname: Cuenca-Estrella
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000201:enzymology / Q000254:growth & development / Q000472:pathogenicity*; D001393:Azoles / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004195:Disease Models, Animal; D025141:Drug Resistance, Fungal; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D007814:Larva; D007915:Lepidoptera; D014774:Virulence
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D005656:Fungal Proteins; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus
keywords: cyp51A gene; isogenic mutants; nonmammalian model