Teikyo University Institute of Medical Mycology, Tokyo, Japan.
Asia International Institute of Infectious Disease Control, Teikyo University, Tokyo, Japan.
Antimicrob Agents Chemother. 2022 Jun 21;66(6):e0005922. doi: 10.1128/aac.00059-22. Epub 2022 May 12.
Trichophyton indotineae causes dermatophytosis that is resistant to terbinafine and azole compounds. The aim of this study was to determine the mechanisms of resistance to itraconazole (ITC) and voriconazole (VRC) in strains of . Two azole-sensitive strains (ITC MIC < 0.125 μg/mL; VRC MIC < 0.06 μg/mL) and four azole-resistant strains (ITC MIC ≥ 0.5 μg/mL; VRC MIC ≥ 0.5 μg/mL) were used for the investigation. The expression of genes encoding multidrug transporters of the ABC family for which orthologs have been identified in Trichophyton rubrum and those of and encoding the targets of azole antifungal compounds were compared between susceptible and resistant strains. and were overexpressed in resistant strains. Only small differences in susceptibility were observed between disruptants and parental strains overexpressing Whole-genome sequencing of resistant strains revealed the creation of a variable number of tandem repeats at the specific position of their genomes in three resistant strains. Downregulation of by RNA interference (RNAi) restored the susceptibility of azole-resistant strains. In contrast, overexpression of cDNA conferred resistance to a susceptible strain of . In conclusion, the reduced sensitivity of strains to azoles is mainly due to the overexpression of resulting from additional copies of this gene.
地丝菌引起的皮肤癣菌病对特比萘芬和唑类化合物具有耐药性。本研究旨在确定 对伊曲康唑（ITC）和伏立康唑（VRC）耐药的机制。使用两种唑类敏感株（ITC MIC<0.125μg/mL；VRC MIC<0.06μg/mL）和四种唑类耐药株（ITC MIC≥0.5μg/mL；VRC MIC≥0.5μg/mL）进行研究。比较了编码 ABC 家族多药转运蛋白的 基因和编码唑类抗真菌化合物靶标的 基因和 基因在敏感株和耐药株中的表达。在耐药株中 和 过表达。与过表达 的亲本菌株相比， 缺失突变体菌株的敏感性差异很小。耐药株的全基因组测序显示，在三个耐药株的基因组特定位置，其基因组中存在数量可变的串联重复。通过 RNA 干扰（RNAi）下调 可恢复唑类耐药株的敏感性。相反， cDNA 的过表达赋予了敏感株对唑类的耐药性。综上所述， 株对唑类药物敏感性降低主要是由于该基因的额外拷贝导致 过表达。
