Comparative Transcriptome Analysis of T. rubrum, T. mentagrophytes, and M. gypseum Dermatophyte Biofilms in Response to Photodynamic Therapy

Abstract

Dermatophyte bio lms frequently count for inadequate responses and resistance to standard antifungal treatment, resulting in refractory chronic onychomycosis infection. Although antimicrobial photodynamic therapy (aPDT) has been clinically found capable of exerting signi cant antifungal effects or even eradicating dermatophyte bio lms, considerably less is known about the molecular mechanism underlying aPDT and the signaling network dysregulation potentially antagonizing photodynamic action. The aim of this study is to elucidate the molecular mechanisms underlining aPDT combating dermatophyte bio lm implicated in recalcitrant onychomycosis and decipher the potential aPDT-elicited detoxi cation process to facilitate the development of more effective photodynamic intervention. We applied genome-wide comparative transcriptome analysis to investigate how aPDT disrupting onychomycosis bio lm formed by three distinct dermatophytes, including T.rubrum, T.mentagrophytes and M.gypseum, the most frequently occurring pathogenic species. In total, 352.13Gb of clean data was obtained for the transcriptomes of dermatophyte bio lms with or without aPDT treatment, resulting in 2422.42 million reads with GC content of 51.84%, covering 99.9%, 98.5% and 99.4% of annotated genes of T. rubrum, T. mentagrophytes and M. gypseum, respectively. The genome-wide orthologous analysis identi ed 6624 transcribed single-copy orthologous genes in all three species, and 36.5%, 6.8% and 17.9% of which were differentially expressed following the aPDT application. Integrative orthology analysis demonstrated up-regulating oxidoreductase activities are highly conserved detoxi cation signaling alteration in response to aPDT across all investigated dermatophyte bio lms. This study provided new insights into the molecular mechanisms underneath anti-dermatophyte bio lm effects of aPDT and successfully identi ed conserved detoxi cation regulation upon the aPDT application.