Inhibitory Effect of Verapamil in the Treatment of Mixed Biofilm of Candida albicans and Staphylococcus aureus

Verapamil (VER) is a calcium channel blocker used to treat cardiovascular diseases. However, some studies also suggest its antimicrobial potential. Changes in calcium abundance in yeasts can lead to decreased expression of transcription factors for genes related to morphology, resistance, and biofilm. Hyphal growth in Candida albicans is necessary for biofilm formation, especially in mixed biofilms with Staphylococcus aureus. This research studied the antibiofilm activity of VER in mixed biofilms of C. albicans SC5314 and S. aureus CCM3953. First, the minimal inhibitory concentration of VER was determined for single-species biofilms. Subsequently, a subinhibitory concentration of VER (1 mM) was tested on mixed biofilms. Biomass was reduced by 20% for C. albicans and 30% for S. aureus. The morphology of C. albicans was altered, and a decrease in S. aureus cells was also observed. qPCR was used to determine changes in HWP1 and ALS3 gene expression in biofilms formed w/wo VER. A decrease in the expression of both genes was observed. In vivo experiments with Galleria mellonella confirmed the antibiofilm activity of VER against mixed infections of C. albicans and S. aureus. These results suggest that VER regulates the morphology of C. albicans, resulting in changes in biofilm composition and the adhesion of S. aureus.