Department of Veterinary Pathobiology, Nihon University College of Bioresource Sciences, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan.
Asian Veterinary Specialist Referral Center, 1F, No. 109, Sec. 4, XingYi Rd., Taipei, 106, Taiwan.
Mycopathologia. 2018 Jun;183(3):623-627. doi: 10.1007/s11046-018-0242-0. Epub 2018 Jan 16.
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.
为了阐明特比萘芬(TRF)耐药的犬小孢子菌(Microsporum canis)菌株的耐药机制,通过实时定量 PCR(RT-qPCR)分析研究了多药耐药(PDR1)、多药耐药(MDR1)、MDR2 和 MDR4 基因的表达,鉴于这些相应蛋白与抗真菌药物以及与外排阻滞剂 FK506 的已知相互作用。在存在 0.14μg/ml TRF 的情况下,与 TRF 敏感株在无 TRF 培养条件下相比,TRF 耐药株中 PDR1、MDR1、MDR2 和 MDR4 基因的表达增加了 2-4 倍。TRF 耐药株对 TRF 单独的 MIC 值>32μg/ml;在外加 FK506 存在下,这种耐药性降低至 8μg/ml 的 MIC,表明 TRF 抑制浓度指数值<0.75。在 TRF 耐药株中检测到外排阻滞剂 FK506 对 TRF 耐药性的附加作用。这些结果表明,该菌株的 TRF 耐药性反映了编码 ABC 转运蛋白基因的过度表达。