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First Isolation of Azole-Resistant Cryptococcus neoformans from Feline Cryptococcosis.
Mycopathologia. 2015 Dec; 180(5-6):427-33.M

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Kano R
Department of Veterinary Pathobiology, Nihon University College of Bioresource Sciences, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan. kanou.rui@nihon-u.ac.jp.
Okubo M
Department of Veterinary Pathobiology, Nihon University College of Bioresource Sciences, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan.
Yanai T
Department of Veterinary Pathology, Faculty of Applied Biological Science, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.
Hasegawa A
Teikyo University Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo, 192-0395, Japan.
Kamata H
Department of Veterinary Pathobiology, Nihon University College of Bioresource Sciences, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan.

MeSH

ATP-Binding Cassette TransportersAnimalsAntifungal AgentsAzolesCat DiseasesCatsCryptococcosisCryptococcus neoformansDrug Resistance, FungalGene ExpressionGene Expression ProfilingMicrobial Sensitivity TestsReal-Time Polymerase Chain ReactionSterol 14-Demethylase

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26162642

Citation

Kano, Rui, et al. "First Isolation of Azole-Resistant Cryptococcus Neoformans From Feline Cryptococcosis." Mycopathologia, vol. 180, no. 5-6, 2015, pp. 427-33.
Kano R, Okubo M, Yanai T, et al. First Isolation of Azole-Resistant Cryptococcus neoformans from Feline Cryptococcosis. Mycopathologia. 2015;180(5-6):427-33.
Kano, R., Okubo, M., Yanai, T., Hasegawa, A., & Kamata, H. (2015). First Isolation of Azole-Resistant Cryptococcus neoformans from Feline Cryptococcosis. Mycopathologia, 180(5-6), 427-33. https://doi.org/10.1007/s11046-015-9919-9
Kano R, et al. First Isolation of Azole-Resistant Cryptococcus Neoformans From Feline Cryptococcosis. Mycopathologia. 2015;180(5-6):427-33. PubMed PMID: 26162642.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - First Isolation of Azole-Resistant Cryptococcus neoformans from Feline Cryptococcosis. AU - Kano,Rui, AU - Okubo,Miki, AU - Yanai,Tokuma, AU - Hasegawa,Atsuhiko, AU - Kamata,Hiroshi, Y1 - 2015/07/11/ PY - 2015/03/10/received PY - 2015/06/30/accepted PY - 2015/7/12/entrez PY - 2015/7/15/pubmed PY - 2016/8/26/medline KW - Azole KW - Cryptococcosis KW - Feline KW - Fluconazole KW - In vitro susceptibility test KW - Resistance SP - 427 EP - 33 JF - Mycopathologia JO - Mycopathologia VL - 180 IS - 5-6 N2 - 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. SN - 1573-0832 UR - https://www.unboundmedicine.com/medline/citation/26162642/First_Isolation_of_Azole_Resistant_Cryptococcus_neoformans_from_Feline_Cryptococcosis_ DB - PRIME DP - Unbound Medicine ER -