Scientists discovered that a small protein (peptide) made by a friendly bacteria can stop the fungus Candida albicans from growing. It does this by sticking to special spots in the fungus’s cell membrane (called lipid rafts) and throwing off many of the fungus’s internal energy and metabolism processes.

Antimicrobial peptides derived from lactic acid bacteria have gained attention for their antibacterial properties, yet their antifungal mechanisms remain underexplored. This research investigated the fungistatic mechanism of antifungal peptide APTs, isolated from Lacticaseibacillus paracasei ALAC-4, against Candida albicans, through interaction with lipid rafts as the potential mediator. Molecular docking revealed stable interactions between APTs and lanosterol 14α-demethylase (RMSF 0.99 Å). Laser scanning confocal microscopy revealed that APTs colocalized with ergosterol in the C. albicans membrane (Pearson's r 0.79). Proteomic analysis identified significant metabolic disruptions, including the downregulation of key enzymes involved in energy and phosphate metabolism, as well as alterations in amino acid and carbohydrate metabolism. Lipid metabolism exhibited marked disruption, as demonstrated by the upregulation of glycerol-3-phosphate dehydrogenase and serine palmitoyl transferase. Furthermore, suppression was observed in both stress response proteins and the ABC transporter pathway. These findings indicate that APTs exerts antifungal activity against C. albicans by interacting with lipid rafts and disrupting multiple metabolic pathways, including energy, phosphate, amino acid, carbohydrate, and lipid metabolism.