Department of Dermatology, University Hospital Jena, Jena, Germany.
Mycoses. 2022 Jan;65(1):97-102. doi: 10.1111/myc.13393. Epub 2021 Nov 16.
The T indotineae population shows a high amount of terbinafine resistant isolates based on different point mutations of squalene epoxidase erg1 (ergosterol) gene. A significant proportion of these isolates also show azole resistance.
Elucidation of the molecular mechanism for azole resistance, especially the identification of mutations in the sterol 14-α demethylase Erg11 genes, which encode for enzymes interacting with azoles.
Sequencing of putative Erg11 genes and analysis of phenotypic resistance pattern using a microplate-laser-nephelometry-based growth assay.
Four different types of Erg11B mutants were detected; two double mutants with Ala230Thr/Asp441Gly, respectively, Ala230/Tyr444His and single mutants with Gly443Glu, Tyr444Cys and Tyr444His. All isolates featured the wild type genotype of Erg11A. All strains demonstrated different combinations of Erg1 and Erg11 genotypes.
Resistance against terbinafine and azoles developed several times independently within the T indotineae population. The challenge for fungal treatment is, therefore, that species identification is not enough for prediction of therapeutic efficacy of antifungals. In the future, it will also become important to analyse genes involved in resistance mechanisms.
基于角鲨烯环氧化酶 erg1（麦角固醇）基因的不同点突变，T 角鲨烯族群体显示出大量特比萘芬耐药分离株。这些分离株中有相当大的比例也表现出唑类耐药性。
阐明唑类耐药的分子机制，特别是鉴定甾醇 14-α 去甲基酶 Erg11 基因（编码与唑类相互作用的酶）的突变。
推测的 Erg11 基因测序和基于微孔板激光散射比浊法的生长测定分析表型耐药模式。
检测到四种不同类型的 Erg11B 突变体；分别为 Ala230Thr/Asp441Gly 的双突变体，Ala230/Tyr444His 和 Gly443Glu、Tyr444Cys 和 Tyr444His 的单突变体。所有分离株均具有 Erg11A 的野生型基因型。所有菌株均表现出 Erg1 和 Erg11 基因型的不同组合。
特比萘芬和唑类药物的耐药性在 T 角鲨烯族群体中多次独立发展。因此，真菌治疗的挑战是，物种鉴定不足以预测抗真菌药物的治疗效果。在未来，分析耐药机制相关基因也将变得很重要。
