关键词: Phe397Leu substitution T. indotineae antifungal susceptibility testing dermatophytes dermatophytosis point mutation squalene epoxidase terbinafine resistance

Mesh : Antifungal Agents / pharmacology Arthrodermataceae / genetics Drug Resistance, Fungal / genetics Humans Microbial Sensitivity Tests Phylogeny Point Mutation Squalene Monooxygenase / genetics Tinea

来  源:   DOI:10.3389/fcimb.2022.851769   PDF(Pubmed)

Abstract:
Drug resistance is one of the major challenges to skin fungal infections, especially in tropical and subtropical infections caused by dermatophytes. This study aimed to determine the antifungal susceptibility of clinically dermatophytes and evaluate point mutations in terbinafine-resistant isolates. A total number of 123 clinical dermatophyte isolates in eight species were evaluated in terms of sensitivity to seven major antifungals. Furthermore, the point mutation in squalene epoxidase (SQLE) gene responsible for terbinafine resistance was studied. The dermatophytes species were identified by morphological characteristics and confirmed by the ITS sequencing. Also, the phylogenetic tree was drawn using the RAxML analyses for 123 dermatophytes isolates. A new XXIX genotype was also found in 4 Trichophyton mentagrophytes isolates. Based on the results obtained, terbinafine was the most effective antifungal drug followed by itraconazole and voriconazole. Trichophyton rubrum and Trichophyton tonsurans were the most susceptible species (MIC50 = 0.01, 0.09 μg/ml), and T. mentagrophytes was the most resistant species (MIC50 = 0.125 μg/ml) to terbinafine. Of the 123 dermatophytes isolates, six isolates showed reduced susceptibility to terbinafine, and only Trichophyton indotineae had a mutation in SQLE gene as a Phe397Leu substitution. Overall, the antifungal susceptibility test is necessary for managing dermatophytosis. These results help physicians to control the course of the disease and provide further insights to select effective drugs for patients with dermatophytosis, especially in tropical and subtropical regions of the world, where dermatophytosis is still a public health problem.
摘要:
耐药性是皮肤真菌感染的主要挑战之一,尤其是由皮肤癣菌引起的热带和亚热带感染。这项研究旨在确定临床皮肤癣菌的抗真菌敏感性,并评估特比萘芬耐药分离株的点突变。根据对七种主要抗真菌药的敏感性,评估了八个物种中的123种临床皮肤癣菌分离株。此外,研究了负责特比萘芬抗性的角鲨烯环氧酶(SQLE)基因的点突变。通过形态特征鉴定皮肤癣菌物种,并通过ITS测序进行确认。此外,使用RAxML分析对123种皮肤癣菌分离株进行系统发育树绘制.在4种毛癣菌植叶植物分离物中也发现了新的XXIX基因型。根据获得的结果,特比萘芬是最有效的抗真菌药物,其次是伊曲康唑和伏立康唑。红色毛癣菌和扁桃体毛癣菌是最易感的物种(MIC50=0.01,0.09μg/ml),而念珠菌是对特比萘芬最具抗性的物种(MIC50=0.125μg/ml)。在123种皮肤癣菌分离物中,六个分离株对特比萘芬的敏感性降低,只有吲哚毛癣菌在SQLE基因中具有Phe397Leu替代的突变。总的来说,抗真菌药敏试验对于治疗皮肤癣菌病是必要的。这些结果有助于医生控制疾病的进程,并提供进一步的见解,为皮肤癣菌病患者选择有效的药物,特别是在世界的热带和亚热带地区,皮肤癣菌病仍然是一个公共卫生问题。
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