Transcriptomic analysis reveals the molecular mechanisms of methylene blue-mediated photodynamic therapy against...

Microsporum canis is a predominant cause of dermatophytosis, presenting a significant therapeutic challenge due to the limitations of conventional antifungal agents and the emergence of drug resistance. Methylene Blue-mediated Photodynamic Therapy (MB-PDT) represents a promising alternative; however, the comprehensive transcriptomic response and specific molecular pathways disrupted by this modality in M. canis remain largely elusive.

This study employed RNA-sequencing (RNA-Seq) to elucidate the global transcriptomic response of M. canis to a sub-inhibitory concentration of MB-PDT. Differentially expressed genes (DEGs) were identified, and their biological functions were characterized via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Furthermore, the expression profiles of key marker genes were validated using qRT-PCR.

A total of 619 DEGs were identified, comprising 341 upregulated and 278 downregulated genes. Functional enrichment analysis highlighted the "ribosome" and "steroid biosynthesis" pathways as the most significantly impacted. The transcriptomic profile suggests that MB-PDT induces multi-target oxidative damage, specifically compromising cell membrane integrity, mitochondrial function, and ribosomal activity. Notably, the expression patterns of key marker genes indicate that M. canis activates an intrinsic programmed cell death (PCD) pathway in response to this irreparable oxidative stress.

Our findings suggest that MB-PDT exerts its antifungal effect against M. canis through a multi-target mechanism that overwhelms cellular repair systems, ultimately triggering the initiation of PCD. This mode of action may mitigate the risk of resistance development, underscoring MB-PDT as a potent therapeutic alternative for the management of dermatophytosis.