Whole Genome Sequence Analysis of Terbinafine Resistant and Susceptible Trichophyton Isolates from Human and Animal...

Trichophyton indotineae, first identified in India, has increasingly been reported in Asia, the Middle East, Europe, and recently in the USA. The global spread of terbinafine-resistant T. indotineae underscores the urgency of the issue. With its ability for human-to-human transmission, it can be considered anthropophilic. However, its highly virulent nature suggests a possible link to zoophilic species, raising the potential for disease transmission from animals. In this study, we have performed whole genome sequencing (WGS) of terbinafine susceptible and resistant Trichophyton species from animal and human origin to understand transmission dynamics of this species. Thirteen isolates of Trichophyton spp. from human (n = 9) and canine (n = 4) origin, respectively from Chandigarh and Bareilly, India, were included in this study. Isolate identification based on ITS extracted from WGS data identified six T. indotineae (ITS genotype VIII) and seven T. interdigitale (ITS genotype II) isolates. WGS single nucleotide polymorhpism (SNP) analysis separated the isolates into two distinct groups, T. indotineae and T. interdigitale and showed the clonal nature of both species. For both species, low SNP differences between isolates from humans and dogs were observed as well as low differences between isolates from Chandigarh and Bareilly, cities >350 km apart from each other. These findings suggest zoonotic transmission, next to fast spread across large distances. The T. indotineae terbinafine-resistant strains exhibited the SQLE^F397L substitution while susceptible strains had the SQLE^S395P substitution or demonstrated a wild-type (WT) SQLE sequence. However, all T. interdigitale strains displayed a WT SQLE sequence despite terbinafine minimum inhibitory concentrations (MICs) ranging between 0.031 to 64 µg/mL.