Dual RNA-Sequencing and Liquid Chromatography-Mass Spectrometry Unveil Specific Insights on the Pathogenicity of Trichophyton mentagrophytes Complex

Abstract

Trichophyton mentagrophytes is increasingly considered to be a public health hazard because it causes the most severe manifestations of dermatophytosis. In this study, we performed a series of studies to determine the pathogenicity of the T. mentagrophytes complex. We show that the T. mentagrophytes complex interacts with keratinocytes through pattern-recognition receptors‒MAPK/noncanonical NF-κB pathways and that the hyphal form of T. mentagrophytes is responsible for the increased inflammatory responses in keratinocytes. Moreover, SN-38 is likely a toxin of T. mentagrophytes that induces apoptosis in keratinocytes both in vivo and in vitro. Our results explain the severe pathogenicity and destructiveness of T. mentagrophytes observed in the clinic and pave the way for designing novel toxin-directed therapies to improve patient outcomes.