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First Isolation of Azole-Resistant Cryptococcus neoformans from Feline Cryptococcosis

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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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Acknowledgments

This study was supported by a grant (“International joint research and training of young researchers for zoonosis control in the globalized world”) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, and by a Nihon University Multidisciplinary Research Grant (2013–2014).

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Authors and Affiliations

  1. Department of Veterinary Pathobiology, Nihon University College of Bioresource Sciences, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan

    Rui Kano, Miki Okubo & Hiroshi Kamata

  2. Department of Veterinary Pathology, Faculty of Applied Biological Science, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan

    Tokuma Yanai

  3. Teikyo University Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo, 192-0395, Japan

    Atsuhiko Hasegawa

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  1. Rui Kano
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  2. Miki Okubo
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  3. Tokuma Yanai
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  4. Atsuhiko Hasegawa
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  5. Hiroshi Kamata
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Correspondence to Rui Kano.

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All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institution and/or national research committee and with the 1964 Helsinki declaration and its amendments or comparable ethical standards.

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Kano, R., Okubo, M., Yanai, T. et al. First Isolation of Azole-Resistant Cryptococcus neoformans from Feline Cryptococcosis. Mycopathologia 180, 427–433 (2015). https://doi.org/10.1007/s11046-015-9919-9

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  • DOI: https://doi.org/10.1007/s11046-015-9919-9

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