title: A New Amino Acid Substitution at G150S in Lanosterol 14-α Demethylase (Erg11 protein) in Multi-azole-resistant Trichosporon asahii.
abstract: The mechanisms of azole resistance in Trichosporon asahii have not yet been fully clarified. We previously showed that T. asahii has the ERG11 gene, coding lanosterol 14-α-demethylase (Erg11 protein; Erg11p), which is the primary target of azoles. A single amino acid substitution at G453R in Erg11p was found to induce changes in the affinity of this enzyme for azoles, especially fluconazole, in vitro. In the present study, we investigated the DNA sequences of the ERG11 gene using six different strains of clinically isolated T. asahii that were highly resistant to multi-azoles, including fluconazole, itraconazole, and voriconazole. All of the T. asahii strains had a point mutation (G448A) that caused a single amino acid substitution at G150S in Erg11p. This amino acid is highly conserved among major fungal pathogens. We identified a new point mutation in the ERG11 gene that is common to clinically isolated azole-resistant T. asahii strains, suggesting that this mutation is associated with the multi-azole resistance of T. asahii.
authors.affiliation: Department of Respiratory Medicine, Fukuoka University Hospital.
authors.forename: Hisako
authors.initials: H
authors.lastname: Kushima
authors.forename: Issei
authors.initials: I
authors.lastname: Tokimatsu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Rie
authors.initials: R
authors.lastname: Kawano
authors.forename: Kentaro
authors.initials: K
authors.lastname: Watanabe
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Kadota
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D004271:DNA, Fungal / Q000235:genetics; D025141:Drug Resistance, Fungal / Q000235:genetics*; D015725:Fluconazole / Q000494:pharmacology; D005800:Genes, Fungal / Q000235:genetics*; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D058886:Sterol 14-Demethylase / Q000737:chemistry* / Q000235:genetics*; D014250:Trichosporon / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D004271:DNA, Fungal; D015725:Fluconazole; D058886:Sterol 14-Demethylase