There has been a considerable upsurge of extensive, treatment recalcitrant, dermatophytosis presenting as tinea corporis and tinea cruris in India since the past few years. Genome analysis of Trichophytonspecies causing severe superficial dermatophytosis in North India confirmed a unique clade related to the T.mentagrophytes/interdigitale complex, seeming to belong to an early diverging clade of the complex. The Indian Trichophyton species genomes were highly related showing only up to 42 SNPs between any two isolates confirming their clonal origin. Other genetic approaches such as ITS sequencing and multigene phylogeny used in this study were contradictory or inconclusive to show the differentiation of these isolates from T. mentagrophytes/T. interdigitale. Remarkably, high rates of resistance to all three commonly used oral antifungals, i.e., 36% for terbinafine (MICs 4 to ≥32 mg/L), 39.5% for fluconazole (MIC range 32 to ≥64 mg/L) and griseofulvin (Geometric mean MIC ≥ 4 mg/L) were observed. Two important amino acid substitutions (Leu393Phe or Phe397Leu) leading to a terbinafine resistant phenotype were found in the squalene epoxidase protein of all tested terbinafine resistant isolates. All 20 examined genomes presented a high mobility group (HMG) domain transcription factor gene corresponding to mating type (+). Of these, three isolates also showed positivity for both alpha-box and HMG in the genome which might indicate hybridization or an incomplete sexual cycle. Therefore, we highlight the potential of this organism to rapidly spread alleles that might be driving antifungal resistance among its population. This new population of Trichophyton with high rates of in vitro antifungal resistance seems to be driving an ongoing outbreak of dermatophytosis in India. Our study highlights difficulties in identifying isolates from the Trichophyton mentagrophytes/interdigitale clade of the genus using currently available molecular tools. High resistance rates of terbinafine warrant further clinical studies to assess its utility in the treatment of dermatophytosis caused by this clonal strain.

中文翻译：

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一个独特的耐多药性克隆毛癣菌种群（不同于毛癣菌/叉毛癣菌复合体）导致印度持续发生的令人震惊的皮肤癣菌爆发：基因组见解和耐药性概况。

在过去的几年中，印度出现了广泛的治疗难治性皮肤癣菌病，表现为股癣和股癣。对印度北部造成严重浅表皮肤皮肤癣菌病的毛癣菌物种进行基因组分析，证实了一个独特的进化枝，与门氏菌/叉指植物复合体有关，似乎属于该复合体的早期分化进化枝。印度毛癣菌物种的基因组高度相关，在任何两个分离株之间仅显示了多达42个SNP，证实了它们的克隆起源。本研究中使用的其他遗传方法（如ITS测序和多基因系统发育）是矛盾的或无结论性的，以表明这些分离株与薄荷茶/ T。的区别。叉指。值得注意的是，对所有三种常用的口服抗真菌药（即 特比萘芬（MICs 4至≥32mg / L）为36％，氟康唑（MIC为32至≥64mg / L）和灰黄霉素（几何平均MIC≥4 mg / L）为39.5％。在所有测试的特比萘芬抗性分离株的角鲨烯环氧酶蛋白中发现了导致特比萘芬抗性表型的两个重要的氨基酸取代（Leu393Phe或Phe397Leu）。所有检查的20个基因组均呈现与交配类型（+）相对应的高迁移率族（HMG）域转录因子基因。其中，三个分离株在基因组中也显示出对α-box和HMG的阳性，这可能表明杂交或不完全的性周期。因此，我们强调了该生物体在其人群中迅速传播可能驱动抗真菌抗性的等位基因的潜力。在印度，这种新的毛癣菌种群具有很高的体外抗真菌抗药性，似乎正在推动皮肤癣菌的持续爆发。我们的研究突显了使用当前可用的分子工具从毛状癣菌/叉指类进化枝中鉴定分离株的困难。特比萘芬的高耐药率值得进一步的临床研究，以评估其在治疗这种克隆菌株引起的皮肤癣菌病中的效用。