Bacteriophages improve the effectiveness of rhamnolipids in combating the biofilm of Candida albicans

Biofilms produced by Candida albicans pose significant therapeutic challenges due to their resistance to conventional antimicrobials. In response, the need for the development of more potent strategies to combat such infections persists. Rhamnolipids (RLs) are biosurfactants with diverse antimicrobial properties. Bacteriophages (phages) are viruses that target specific bacterial strains, although recent studies have shown that they may also potentially affect biofilm formation by fungi and yeasts. This study investigated the combined antimicrobial effect of RLs and bacteriophages against C. albicans biofilms, focusing on their anti-adhesive and inhibitory effects on biofilm development. RT-PCR assays were used to analyze gene modulation in C. albicans biofilm formation in response to RLs and phage treatments. Additionally, hyphae formation in the presence of RLs, phages, and their mixtures was examined using fluorescence microscopy. The results demonstrated that the combined treatment of RLs and bacteriophages significantly reduced biofilm formation compared to individual treatments. The combination of 200 mg/L rhamnolipid with BF9 phage achieved a 94.8% decrease in biofilm formation. This synergy was confirmed in subsequent models, with rhamnolipids at the same concentration and phage LO5/1f nearly completely inhibiting biofilm formation (~ 96%). Gene expression analysis revealed a profound downregulation of key biofilm-associated genes when Candida cells were treated with 200 mg/L RLs and four phages (BF17, L05/1f, JG004, FD). The results of this study suggest the potential of combining RLs and bacteriophages in combating C. albicans biofilms, indicating a promising perspective for future therapeutic approaches, offering renewed hope in the battle against resilient infections.