title: In vitro fluconazole susceptibility of 1,903 clinical isolates of Candida albicans and the identification of ERG11 mutations.
abstract: Abstract Fluconazole resistance of Candida albicans has been reported to be the result of one or more specific point mutations in ERG11 gene. In this study, we amplified and sequenced the entire ERG11 coding sequence of 72 isolates of C. albicans to search for possible mutations. Twenty-seven silent mutations and 14 missense mutations were identified. While the mutations K342R and V437I were found as single-amino-acid changes in Erg11p, other mutations were detected simultaneously in individual isolates. Several different clinical isolates had the same pattern of multiple amino acid alternations: (1) A114S with Y257H was identified in 11 resistant and 3 susceptible dose-dependent isolates without any other silent mutation and may be associated with resistance; (2) Y132H combined with G450E was identified in two fluconazole-resistant isolates and is known to contribute to resistance; and (3) the coexistence of D116E, K128T, Y132H, and G465S was first described in five reduced-susceptibility isolates, but the correlation of this pattern with resistance is still uncertain. These data indicate that multiple amino acid substitutions in Erg11p were found frequently in clinical isolates and may be associated with fluconazole resistance.
authors.affiliation: Department of Medical Microbiology, Nanchang University, Nanchang, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ying
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xuefei
authors.initials: X
authors.lastname: Hu
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Cai
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Guilin
authors.initials: G
authors.lastname: Jin
authors.forename: Jieyu
authors.initials: J
authors.lastname: Zhang
authors.forename: Jingyi
authors.initials: J
authors.lastname: Zhang
authors.forename: Jinhui
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Huang
mesh_terms: D019943:Amino Acid Substitution; D000935:Antifungal Agents / Q000494:pharmacology*; D001483:Base Sequence; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D015725:Fluconazole; D003577:Cytochrome P-450 Enzyme System