Aspergillus fumigatus Intrinsic Fluconazole Resistance Is Due to the Naturally Occurring T301I Substitution in Cyp51Ap | Zendy

Florencia Leonardelli | Zendy; Daiana Macedo | Zendy; Catiana Dudiuk | Zendy; Matías S. Cabeza | Zendy; Soledad Gamarra | Zendy; Guillermo GarcíaEffrón | Zendy

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Aspergillus fumigatus Intrinsic Fluconazole Resistance Is Due to the Naturally Occurring T301I Substitution in Cyp51Ap

Author(s) -

Florencia Leonardelli,

Daiana Macedo,

Catiana Dudiuk,

Matías S. Cabeza,

Soledad Gamarra,

Guillermo GarcíaEffrón

Publication year - 2016

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.00905-16

Subject(s) - aspergillus fumigatus , fluconazole , microbiology and biotechnology , candida albicans , biology , azole , corpus albicans , mutant , fungal protein , fungi imperfecti , gene , genetics , antifungal

Aspergillus fumigatus intrinsic fluconazole resistance has been demonstrated to be linked to theCYP51A gene, although the precise molecular mechanism has not been elucidated yet. Comparisons betweenA. fumigatus Cyp51Ap andCandida albicans Erg11p sequences showed differences in amino acid residues already associated with fluconazole resistance inC. albicans . The aim of this study was to analyze the role of the natural polymorphism I301 inAspergillus fumigatus Cyp51Ap in the intrinsic fluconazole resistance phenotype of this pathogen. The I301 residue inA. fumigatus Cyp51Ap was replaced with a threonine (analogue to T315 atCandida albicans fluconazole-susceptible Erg11p) by changing one single nucleotide in theCYP51A gene. Also, aCYP51A knockout strain was obtained using the same parental strain. Both mutants' antifungal susceptibilities were tested. The I301T mutant exhibited a lower level of resistance to fluconazole (MIC, 20 μg/ml) than the parental strain (MIC, 640 μg/ml), while no changes in MIC were observed for other azole- and non-azole-based drugs. These data strongly implicate theA. fumigatus Cyp51Ap I301 residue in the intrinsic resistance to fluconazole.

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