Sterilization Activity and Mechanism of 3,4,5‐Trihydroxy‐biphenyl From Sorbus pohuashanensis Against Candida glabrata

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Candida glabrata is a common opportunistic pathogen in clinical settings, often exhibiting resistance to antifungal therapies. Exploring novel compounds that inhibit C. glabrata holds significant clinical and translational value. Our team recently identified a biphenyl compound 3,4,5-trihydroxy-biphenyl (THB) from Sorbus pohuashanensis; however, its antifungal activity against C. glabrata and the associated molecular response remain unclear. This study represents the first analysis of THB against C. glabrata based on the minimum inhibitory concentration (MIC) and offers preliminary insights into the molecular mechanism of action through transcriptomic sequencing. The results demonstrated that the MIC of THB against C. glabrata was 1.77 µg/mL. Transcriptomic sequencing revealed 785 differentially expressed genes (DEGs) following treatment of C. glabrata with THB, with 332 genes significantly upregulated and 453 genes significantly downregulated. Gene ontology (GO) analysis indicated that the DEGs were primarily associated with cellular processes, metabolic pathways, and cellular component (CC) organization or biogenesis. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these DEGs were primarily enriched in pathways related to translation, carbon metabolism, amino acid metabolism, and energy metabolism. qRT-PCR results confirmed similar expression patterns for mak16, brx1, CAGL0C03223g, and CAGL0E05984g as observed in the RNA-Seq analysis. These findings indicate that THB has potent in vitro antifungal activity against C. glabrata, supporting its potential as a lead compound for further antifungal investigation.

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