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

Abstract

Abstract Dermatophyte biofilms 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 significant antifungal effects or even eradicating dermatophyte biofilms, 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 biofilm implicated in recalcitrant onychomycosis and decipher the potential aPDT-elicited detoxification process to facilitate the development of more effective photodynamic intervention. We applied genome-wide comparative transcriptome analysis to investigate how aPDT disrupting onychomycosis biofilm 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 biofilms 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 identified 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 detoxification signaling alteration in response to aPDT across all investigated dermatophyte biofilms. This study provided new insights into the molecular mechanisms underneath anti-dermatophyte biofilm effects of aPDT and successfully identified conserved detoxification regulation upon the aPDT application.