Department of Veterinary Microbiology, Faculty of Veterinary Medicine, Institute of Preclinical Veterinary Sciences, University of Life Sciences, Akademicka 12, 20-033, Lublin, Poland.
Department of Mycology and Genetics, Faculty of Biological Sciences, Institute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland.
Braz J Microbiol. 2021 Dec;52(4):2439-2446. doi: 10.1007/s42770-021-00585-1. Epub 2021 Aug 5.
Dermatophytes are a group of eukaryotic microorganisms characterized by high capacity to colonize keratinized structures such as the skin, hair, and nails. Over the past years, the incidence of infections caused by zoophilic species, e.g., Trichophyton verrucosum, has been increasing in some parts of the world, especially in Europe. Moreover, the emergence of recalcitrant dermatophytoses and in vitro resistant dermatophytes has become a cause of concern worldwide. Here, we analyzed the mechanisms underlying resistance to fluconazole among clinical isolates of T. verrucosum. Quantitative RT-PCR was carried out to determine the relative expression levels of mRNA transcripts of ERG3, ERG6, and ERG11 genes in the fungal samples using the housekeeping gene GAPDH as a reference. Our results showed that the upregulation of the ERG gene expression is a possible mechanism of resistance to fluconazole in this species. Furthermore, ERG11 is the most statistically significantly overexpressed gene in the pool of fluconazole-resistant T. verrucosum isolates. Additionally, we have demonstrated that exposure to fluconazole increases the levels of expression of ERG genes in fluconazole-resistant isolates of T. verrucosum. In conclusion, this study has shown one of the possible mechanisms of resistance to fluconazole among zoophilic dermatophytes, which involves the maintenance of high levels of expression of ERG genes after drug exposure.
皮肤癣菌是一组真核微生物，其特征是具有高度定植角蛋白结构（如皮肤、毛发和指甲）的能力。在过去的几年中，某些地区（尤其是欧洲）引起亲动物性物种感染的病例（例如疣状毛癣菌）的发病率一直在上升。此外，抗药性和体外耐药性皮肤癣菌的出现已成为全球关注的问题。在这里，我们分析了临床分离的疣状毛癣菌对氟康唑耐药的机制。使用管家基因 GAPDH 作为参照，通过定量 RT-PCR 确定真菌样品中 ERG3、ERG6 和 ERG11 基因的 mRNA 转录本的相对表达水平。我们的结果表明，ERG 基因表达的上调可能是该物种对氟康唑耐药的一种机制。此外，在氟康唑耐药的疣状毛癣菌分离株中，ERG11 是统计学上表达上调最显著的基因。此外，我们已经证明，氟康唑暴露会增加氟康唑耐药的疣状毛癣菌分离株中 ERG 基因的表达水平。总之，这项研究表明了亲动物性皮肤癣菌对氟康唑耐药的一种可能机制，即药物暴露后 ERG 基因的高表达水平得以维持。
