Abstract：
Treatment-resistant dermatophytosis caused by the members of the Trichophyton mentagrophytes/Trichophyton interdigitale species group (TMTISG) is increasing worldwide. We aimed to determine the prevalence of TMTISG in patients with dermatophytosis in two centers from north of Iran and detect the possible mutations in the squalene epoxidase (SQLE) gene in relevant terbinafine (TRB) resistant pathogenic isolates. From November 2021 to December 2022, 1960 patients suspected to dermatophytosis and referred to two mycology referral laboratories in the north of Iran were included in the study. Identification of all dermatophyte isolates was confirmed by RFLP of rDNA internal transcribed spacer (ITS) regions. Antifungal susceptibility testing against five common antifungals using the CLSI-M38-A3 protocol was performed. The TMTISG isolates resistant to TRB, were further analyzed to determine the possible mutations in the SQLE gene. Totally, 647 cases (33%) were positive for dermatophytosis of which 280 cases (43.3%) were identified as members of TMTISG. These were more frequently isolated from tinea corporis 131 (44.56%) and tinea cruris 116 (39.46%). Of 280 TMTISG isolates, 40 (14.3%) were resistant to TRB (MIC ≥ 4 µg/mL), all found to be T. indotineae in ITS sequencing. In SQLE sequencing 34 (85%) of TRB-resistant isolates had coincident mutations of Phe397Leu and Ala448Thr whereas four and two isolates had single mutations of Phe397Leu and Leu393Ser, respectively. Overall, the resistance of Iranian TMTISG isolates to TRB greatly occurred by a mutation of Phe397Leu in the SQLE gene as alone or in combination with Ala448Thr. Nevertheless, for the occurrence of in vitro resistance, only the presence of Phe397Leu mutation seems to be decisive.
摘要：
在世界范围内，由毛癣菌/毛癣菌物种组（TMTISG）的成员引起的抗治疗性皮肤癣菌病正在增加。我们旨在确定伊朗北部两个中心皮肤癣菌病患者中TMTISG的患病率，并检测相关特比萘芬（TRB）耐药病原分离株中角鲨烯环氧酶（SQLE）基因的可能突变。从2021年11月到2022年12月，1960名疑似皮肤癣菌病并转诊到伊朗北部两个真菌学转诊实验室的患者被纳入研究。通过rDNA内部转录间隔区（ITS）区域的RFLP确认了所有皮肤癣菌分离株的鉴定。使用CLSI-M38-A3方案对五种常见抗真菌药物进行抗真菌药敏试验。TMTISG分离株对TRB具有抗性，进一步分析以确定SQLE基因中可能的突变。完全正确,647例（33％）皮肤癣菌病阳性，其中280例（43.3％）被确定为TMTISG成员。这些更常见的是从体癣131（44.56％）和股癣116（39.46％）中分离出来的。在280个TMTISG分离株中，40（14.3%）对TRB具有抗性（MIC≥4µg/mL），在ITS测序中发现全部为吲哚虫。在SQLE测序中，34个（85％）的TRB抗性分离株具有Phe397Leu和Ala448Thr的同时突变，而四个和两个分离株具有Phe397Leu和Leu393Ser的单突变，分别。总的来说,伊朗TMTISG分离株对TRB的抗性很大程度上是由于SQLE基因中Phe397Leu的突变，单独或与Ala448Thr联合使用。然而，对于体外抗性的发生，只有Phe397Leu突变的存在似乎是决定性的。
