title: In vitro resistance of Aspergillus fumigatus to azole farm fungicide.
abstract: Azole resistance in Aspergillus fumigatus is mainly due to a point mutation in the 14α-sterol demethylase (CYP51A) gene, which encodes the target of azole fungicides. Moreover, overexpression of CYP51B or multidrug resistance (MDR) gene is supposedly related to the mechanism of azole resistance in A. fumigatus. In this study, we tried to induce resistance to tetraconazole, an azole fungicide, in strains of A. fumigatus from a farm and then investigated mutation and expression of their CYP51A, CYP51B, and multidrug resistance (MDR) genes. Three tetraconazole resistant strains were induced and their minimum inhibitory concentration (MIC) for tetraconazole was 145 mg/L. However, the MICs of itraconazole (ITZ), posaconazole (POS), and voriconazole (VRZ) obtained by an E-test of the three tetraconazole resistant strains were 0.064-0.19 mg/L for ITZ, 0.023-0.32 mg/L for POS, and 0.047-0.064 mg/L for VRZ. No gene mutations were detected in the CYP 51A sequence amplified in these strains. RT-PCR of cyp51A and cyp51B indicated that the tetraconazole resistant strains more highly expressed these genes than the susceptible strain in tetraconazole containing medium.
authors.affiliation: College of Bioresource Sciences, Nihon University, 1866 Kameino, Fuzisawa, Kanagawa 252-8510, Japan. Electronic address: kanou.rui@nihon-u.ac.jp.
authors.forename: Rui
authors.initials: R
authors.lastname: Kano
authors.affiliation: College of Bioresource Sciences, Nihon University, 1866 Kameino, Fuzisawa, Kanagawa 252-8510, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Sobukawa
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi 5274-8555, Japan.
authors.forename: Somay Yamagata
authors.initials: SY
authors.lastname: Murayama
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi 5274-8555, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Hirose
authors.affiliation: School of Dentistry of Matsudo, Nihon University, 2-870-1 Sakaechonishi, Matsudo, Chiba 271-8587, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi 5274-8555, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kosuge
authors.affiliation: Teikyo University Institute of Medical Mycology, 539 Otsuka, Hachioji, Tokyo 192-0395, Japan.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Hasegawa
authors.affiliation: College of Bioresource Sciences, Nihon University, 1866 Kameino, Fuzisawa, Kanagawa 252-8510, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamata
mesh_terms: D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics*; D001393:Azoles / Q000494:pharmacology*; D025141:Drug Resistance, Fungal; D004783:Environmental Microbiology; D000072480:Farms; D005659:Fungicides, Industrial / Q000494:pharmacology*
chemical_list: D001393:Azoles; D005659:Fungicides, Industrial
keywords: Aspergillus fumigatus; Farm fungicide; Resistance