title: Does farm fungicide use induce azole resistance in Aspergillus fumigatus?
abstract: Azole resistance of Aspergillus fumigatus isolates has been reported worldwide and it would appear to be mainly due to a point mutation in the 14α-sterol demethylase (CYP51A) gene, which is the target enzyme for azoles. The mutation has been confirmed in isolates from patients who received long-term itraconazole (ITZ) therapy and from agricultural fields where high levels of azole fungicides were employed. However, the relationship between farm environments and azole-resistant A. fumigatus has not been fully studied. In this investigation, 50 isolates of A. fumigatus were obtained from a farm where tetraconazole has been sprayed twice a year for more than 15 years. The mean minimum inhibitory concentration (MIC) of isolates was 0.74 (0.19-1.5) mg/L against ITZ, which was below the medical resistance level of ITZ. The sequence of CYP51A from isolates indicated no gene mutations in isolates from the farm. Antifungal susceptibility of isolates to tetraconazole showed that spraying with tetraconazole did not induce resistance to tetraconazole or ITZ in A. fumigatus.
authors.affiliation: College of Bioresource Sciences, Nihon University, 1866 Kameino, Fuzisawa, Kanagawa 252-8510, Japan 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: Erina
authors.initials: E
authors.lastname: Kohata
authors.affiliation: College of Bioresource Sciences, Nihon University, 1866 Kameino, Fuzisawa, Kanagawa 252-8510, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tateishi
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: Yasuko
authors.initials: Y
authors.lastname: Shibata
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: College of Bioresource Sciences, Nihon University, 1866 Kameino, Fuzisawa, Kanagawa 252-8510, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Inoue
authors.affiliation: College of Bioresource Sciences, Nihon University, 1866 Kameino, Fuzisawa, Kanagawa 252-8510, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamata
authors.affiliation: Teikyo University Institute of Medical Mycology, 539 Otsuka, Hachioji, Tokyo 192-0395, Japan.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Hasegawa
mesh_terms: D000383:Agriculture / Q000379:methods; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D001393:Azoles / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D025141:Drug Resistance, Fungal; D004783:Environmental Microbiology; D005656:Fungal Proteins / Q000235:genetics; D005659:Fungicides, Industrial / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D017354:Point Mutation
chemical_list: D001393:Azoles; D005656:Fungal Proteins; D005659:Fungicides, Industrial; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus
keywords: Aspergillus fumigatus; farm fungicide; resistance; tetraconazole