title: First Isolation of Azole-Resistant Cryptococcus neoformans from Feline Cryptococcosis.
abstract: We report here, to the best of our knowledge, the first description of an in vitro fluconazole (FLZ)-resistant Cryptococcus neoformans var. grubii from a case of feline cryptococcosis. In vitro testing demonstrated that this isolate was resistant to FLZ (minimum inhibitory concentration, MIC, of 128 μg/ml) but remained susceptible to amphotericin B (0.064 µg/ml), itraconazole (0.38 µg/ml), voriconazole (0.023 µg/ml), and posaconazole (0.125 µg/ml). The predicted amino acid sequence of the lanosterol 14-α demethylase (ERG11) protein in the isolate was identical to that of the C. neoformans var. grubii reference strain, indicating that resistance was not mediated by mutation of the target gene's open reading frame. The RT-qPCR analysis for ERG11 and ATP-binding cassette (ABC) transporter-encoding gene (AFR1) indicated that the isolate increased transcription factor function of ERG11 and AFR1 than that of FLZ-susceptive strains. This observation, in combination with the lack of resistance to other azoles (that is, lack of crossresistance), suggests that resistance in our isolate was the result of overexpression of the endogenous ERG11 and ABC transporter.
authors.affiliation: Department of Veterinary Pathobiology, Nihon University College of Bioresource Sciences, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan. kanou.rui@nihon-u.ac.jp.
authors.forename: Rui
authors.initials: R
authors.lastname: Kano
authors.affiliation: Department of Veterinary Pathobiology, Nihon University College of Bioresource Sciences, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Okubo
authors.affiliation: Department of Veterinary Pathology, Faculty of Applied Biological Science, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.
authors.forename: Tokuma
authors.initials: T
authors.lastname: Yanai
authors.affiliation: Teikyo University Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo, 192-0395, Japan.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Hasegawa
authors.affiliation: Department of Veterinary Pathobiology, Nihon University College of Bioresource Sciences, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamata
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D002371:Cat Diseases / Q000382:microbiology*; D002415:Cats; D003453:Cryptococcosis / Q000382:microbiology / Q000662:veterinary*; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification*; D025141:Drug Resistance, Fungal; D015870:Gene Expression; D020869:Gene Expression Profiling; D008826:Microbial Sensitivity Tests; D060888:Real-Time Polymerase Chain Reaction; D058886:Sterol 14-Demethylase / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D001393:Azoles; D058886:Sterol 14-Demethylase
keywords: Azole; Cryptococcosis; Feline; Fluconazole; In vitro susceptibility test; Resistance