Journal Article

Epidemiological trends, antifungal drug susceptibility and SQLE point mutations in etiologic species of human dermatophytosis in Al-Diwaneyah, Iraq

Mahmood, Hussein R., Salehi, Zahra, Shams-Ghahfarokhi, Masoomeh, Razzaghi-Abyaneh, Mehdi

2024

Overview

Dermatophytes show a wide geographic distribution and are the main causative agents of skin fungal infections in many regions of the world. Recently, their resistance to antifungal drugs has led to an obstacle to effective treatment. To address the lack of dermatophytosis data in Iraq, this study was designed to investigate the distribution and prevalence of dermatophytes in the human population and single point mutations in squalene epoxidase gene ( SQLE ) of terbinafine resistant isolates. The identification of 102 dermatophytes isolated from clinical human dermatophytosis was performed through morphological and microscopic characteristics followed by molecular analysis based on ITS and TEF-1α sequencing. Phylogeny was achieved through RAxML analysis. CLSI M38-A2 protocol was used to assess antifungal susceptibility of the isolates to four major antifungal drugs. Additionally, the presence of point mutations in SQLE gene, which are responsible for terbinafine resistance was investigated. Tinea corporis was the most prevalent clinical manifestation accounting for 37.24% of examined cases of dermatophytosis. Based on ITS , T. indotineae (50.98%), T. mentagrophytes (19.61%) , and M. canis (29.41%) was identified as an etiologic species. T. indotineae and T. mentagrophytes strains were identified as T. interdigitale based on TEF-1α . Terbinafine showed the highest efficacy among the tested antifungal drugs. T. indotineae and T. mentagrophytes showed the highest resistance to antifungal drugs with MICs of 2–4 and 4 μg/mL, while M. canis was the most susceptible species. Three of T. indotineae isolates showed mutations in SQLE gene Phe 397 Leu substitution. A non-previously described point mutation, Phe 311 Leu was identified in T. indotineae and mutations Lys 276 Asn, Phe 397 Leu and Leu 419 Phe were diagnosed in T. mentagrophytes XVII. The results of mutation analysis showed that Phe 397 Leu was a destabilizing mutation; protein stability has decreased with variations in pH, and point mutations affected the interatomic interaction, resulting in bond disruption. These results could help to control the progression of disease effectively and make decisions regarding the selection of appropriate drugs for dermatophyte infections.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/1647 / 631/326 / Adolescent / Adult / Aged / Antifungal agents / Antifungal Agents - pharmacology / Antifungal susceptibility / Arthrodermataceae - drug effects / Arthrodermataceae - genetics / Arthrodermataceae - isolation & purification / Arthrodermataceae - pathogenicity / Child / Dermatomycosis / Dermatophytes / Dermatophytosis / Drug resistance / Drug Resistance, Fungal - genetics / Drugs / Epidemiology / Female / Fungal Proteins - genetics / Geographical distribution / Human populations / Humanities and Social Sciences / Humans / Iraq / Iraq - epidemiology / Male / Microbial Sensitivity Tests / Middle Aged / multidisciplinary / Mutation / Phylogeny / Physical characteristics / Point Mutation / Science / Science (multidisciplinary) / SQLE mutation / Squalene / Squalene epoxidase / Squalene Monooxygenase - genetics / Terbinafine / Terbinafine - pharmacology / Terbinafine - therapeutic use / Terbinafine resistance / Tinea - drug therapy / Tinea - epidemiology / Tinea - microbiology / Tinea corporis / Young Adult