Resistance Mechanism in a Terbinafine-Resistant Strain of Microsporum canis
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To clarify the terbinafine (TRF) resistance mechanism in a TRF-resistant strain of Microsporum canis, the expression of the pleiotropic drug resistance (PDR1), multidrug resistance (MDR1), MDR2 and MDR4 genes were investigated by real-time quantitative PCR (RT-qPCR) analysis, given the known interaction of the corresponding proteins with antifungals and with the efflux blocker FK506. The expression of the PDR1, MDR1, MDR2 and MDR4 genes was 2–4 times higher in the TRF-resistant strain grown in the presence of 0.14 µg/mL of TRF than in TRF-susceptible strains cultured in the absence of TRF. The TRF-resistant strain exhibited MICs of > 32 µg/mL for TRF alone; this resistance was attenuated to an MIC of 8 µg/mL in the presence of FK506, indicating that the TRF inhibitory concentration index value was < 0.75. The additive effect of the efflux blocker FK506 on TRF resistance was detected in the TRF-resistant strain. These results indicated that the TRF resistance in this strain reflects overexpression of genes encoding ABC transporter proteins.
KeywordsABC transporter Microsporum canis FK506 Resistance Terbinafine
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.
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The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.
- 1.Moriello KA, DeBoer DJ. Dermatophytosis. In: Greene CE, editor. Infectious diseases of the dog and cat. 4th ed. St. Louis: Saunders Elsevier; 2012. p. 588–602.Google Scholar
- 2.Reiss E, Shadomy HJ, Lyon GMIII (2012) Dermatophytosis. In: Fundamental medical mycology. Wiley, New Jersey pp 527–565.Google Scholar
- 5.Hsiao Y-H, Kumagawa M, Rui Kano, Han HS, Chen C. Terbinafine resistance clinical isolate of Microsporum canis from a cat in Asia. J Vet Med Sci. 2017; Submitted.Google Scholar
- 9.NCCLS; National Committee for Clinical and Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of yeasts. In: Approved standard M27-A2. Wayne: National Committee for Clinical Laboratory Standards; 2002.Google Scholar
- 15.Yamada T, Maeda M, Alshahni MM, Tanaka R, Yaguchi T, Bontems O, Salamin K, Fratti M, Monod M. Terbinafine resistance of trichophyton clinical isolates caused by specific point mutations in the squalene epoxidase gene. Antimicrob Agents Chemother. 2017. https://doi.org/10.1128/aac.00115-17.CrossRefPubMedPubMedCentralGoogle Scholar