Transcriptomics uncovers key genes for photodynamic killing on Trichosporon asahii biofilms

The escalating threat of antifungal resistance stemming from Trichosporon asahii ( T. asahii ) biofilms necessitates the pursuit of innovative therapeutic strategies. Among these approaches, 5-aminolevulinic acid (ALA) photodynamic therapy (PDT), an emerging therapeutic modality, has exhibited promising potential in eradicating T. asahii biofilms. To delve deeper into the efficacy of ALA-PDT in eliminating T. asahii biofilms, we conducted a comprehensive transcriptional analysis utilizing transcriptome sequencing (RNA-Seq). Notably, ALA-PDT demonstrated a profound inhibitory effect on the viability of T. asahii biofilms. Therefore, we selected T. asahii biofilms subjected to ALA-PDT treatment for transcriptome analysis and compared them to the control group. Our investigation unveiled 2,720 differentially expressed genes (DEGs) following exposure to ALA-PDT. Subsequent meticulous scrutiny allowed for the annotation of genes with a ≥ 2-fold change in transcription, focusing on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Particularly noteworthy were the upregulated genes associated with oxidation-reduction processes, oxidoreductase activity, and catalytic activity. Conversely, the downregulated genes were linked to ATP binding, protein phosphorylation, and protein kinase activity. Additionally, we observed a surge in the transcription of genes that may be involved in oxidative stress (A1Q1_05494) as well as genes that may be involved in morphogenesis and biofilm formation (A1Q1_04029, A1Q1_01345, A1Q1_08069, and A1Q1_01456) following ALA-PDT treatment. Collectively, our findings underscore the substantial impact of ALA-PDT on the transcriptional regulation of genes related to oxidative stress, morphogenesis, and biofilm formation, paving the way for novel therapeutic avenues in combating T. asahii biofilms.