Inhibitory effect of berberine hydrochloride against Candida albicans and the role of the HOG-MAPK pathway

Berberine hydrochloride (BH), an active component of Coptis chinensis and other plant taxa, has broad antimicrobial activity and may be useful for the treatment of Candida infections. In this study, the mechanisms underlying the inhibitory effect of BH against Candida albicans were evaluated, with a focus on the high-osmolarity glycerol mitogen-activated protein kinase (HOG-MAPK) pathway, which regulates multiple physiological functions. BH (256 and 64 μg ml-1) significantly increased intracellular glycerol and ROS levels in C. albicans, inhibited germ tube and hyphal formation, and increased chitin and β-1,3-glucan exposure on the cell wall. The inhibitory effect of BH was positively correlated with its concentration, and the inhibitory effect of 256 μg ml-1 BH was greater than that of 4 μg ml-1 fluconazole (FLC). Furthermore, RT-PCR analysis showed that 256 and 64 μg ml-1 BH altered the HOG-MAPK pathway in C. albicans. In particular, the upregulation of the core genes, SLN1, SSK2, HOG1, and PBS2 may affect the expression of key downstream factors related to glycerol synthesis and osmotic pressure (GPD1), ROS accumulation (ATP11 and SOD2), germ tube and hyphal formation (HWP1), and cell wall integrity (CHS3 and GSC1). BH affects multiple biological processes in C. albicans; thus, it can be an effective alternative to conventional azole antifungal agents.