Berberine Hydrochloride Enhances the Fluconazole Susceptibility of Candida albicans through Multiple Targets.

Candida albicans is ubiquitous on human mucosal surfaces and easy to cause infectious diseases. The widespread use of antifungal drugs has led to the increasing drug resistance of C. albicans, posing a significant challenge to clinical treatment. Berberine hydrochloride (BBH), a quaternary ammonium alkaloid isolated from Coptidis Rhizoma, exhibits broad-spectrum antifungal activity. This study explored the antifungal effect and mechanism of BBH combined with fluconazole (FLC) against drug-resistant C. albicans. Results showed that BBH could enhance the antifungal effect of FLC against the drug-resistant C. albicans. Additionally, BBH combined with FLC significantly disrupted the cell wall integrity, inhibited the formation of biofilms and hyphae, and increased the ROS levels. Transcriptome sequencing further elucidated the inhibitory mechanism of BBH combined with FLC against drug-resistant C. albicans, which primarily by affecting metabolic pathways such as cell wall biosynthesis, superoxide metabolism, and monooxygenase activity. Key genes associated with these pathways, including CHS1, SUN41, CTA1, SOD5, and HWP1, were significantly downregulated. This study primarily reveals that BBH combined with FLC exhibits significant antifungal effects against drug-resistant C. albicans. This provides new therapeutic insights and potential drug combination schemes for clinical treatment of drug-resistant C. albicans infections.