The emergence and worldwide spread of the species Trichophyton indotineae causing difficult-to-treat dermatophytosis: A new challenge in the management of dermatophytosis

Abstract

Superficial fungal infections of the skin, hair, and nails are the fourth most common cause of human disease affecting 20% to 25% of the world’s population [1]. Dermatophytosis is a superficial fungal infection caused by dermatophytic fungi that affect skin and the keratinized structures (hair and nails) arising from it. Dermatophytes, especially from the genera Trichophyton, cause the majority of superficial mycoses. These infections result in considerable morbidity and economic burden on the healthcare system [2]. In recent years, an alarming increase in the frequency of recalcitrant superficial fungal infections caused by novel species of Trichophyton, i.e., Trichophyton indotineae has been witnessed worldwide [3–24]. Importantly, the majority of the T. indotineae strains exhibit alteration in the squalene epoxidase (SQLE) gene that confers high terbinafine (TRB) resistance [3–5,7,10,11,13–17,19,21,22,25–28]. TRB is a first-line drug for treatment of moderate to severe dermatophytosis, and patients with T. indotineae infections typically show decreased effectiveness of oral therapy with this antifungal [29]. T. indotineae has been designated recently in the year 2020 as a distinct species independent of Trichophyton interdigitale and Trichophyton mentagrophytes on the basis of internal transcribed spacer (ITS) region sequencing of 2 highly TRB-resistant Trichophyton strains from a Nepali patient and an Indian patient [5]. On ITS phylogenetic analysis, TRB-resistant Indian strains cluster independently of the clusters of the T. interdigitale and T. mentagrophytes strains and differ in 2 to 3 single-nucleotide polymorphisms (SNPs) from T. mentagrophytes/T. interdigitale strains [5]. Subsequently, multigene polyphasic analysis of a larger data set of T. indotineae strains showed that these strains have distinct sequences of the high mobility group (HMG) gene as compared to T. mentagrophytes s. str. and T. interdigitale s. str [30]. Unlike the infections caused by T. mentagrophytes and T. interdigitale, T. indotineae often presents with extensive skin lesions and a chronic relapsing course. The whole genome sequencing analysis of 20 T. indotineae strains demonstrate that this new species is distinct clonal offshoot of T. mentagrophytes/T. interdigitale spp. complex. Thus, naming of this emerging antifungal-resistant species was essential as it could not be unambiguously identified as either T. mentagrophytes or T. interdigitale based on ITS sequencing, mycological and physiological characteristics.