Integrating transcriptomics and molecular simulation to reveal the antifungal mechanism of borneol against Candida albicans

Natural plant-derived molecules are emerging as promising alternatives to chemical preservatives. Among these, the phytochemical borneol has been shown to inhibit the growth of common foodborne bacteria, but its antifungal activity and underlying mechanisms remain largely unexplored. This study aims to investigate the antifungal properties of borneol and its mechanisms of action against Candida albicans , a foodborne fungus that poses a significant threat to food safety. The results demonstrated that the antifungal efficacy of borneol against Candida albicans was concentration-dependent at the tested time points. Transcriptomic analysis and electron microscopy revealed that borneol primarily targets cell membranes to exert its antifungal effects. Further experiments showed that borneol specifically binds to membrane proteins, particularly chitin synthases 1, 2, and 3, inhibiting chitin biosynthesis and disrupting cellular integrity. Molecular dynamics simulations indicated that borneol diffuses passively from the aqueous phase into the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphorylcholine bilayer membrane, where it preferentially aggregates in hydrophobic regions, altering the bilayer's thickness and fluidity. Notably, this aggregation likely plays a key role in influencing the structure and function of membrane proteins. Lipidomics analysis further confirmed that borneol disrupts cell membrane integrity, leading to the loss of glycerophosphocholines and glycerophosphoethanolamines lipids. As borneol alters membrane structure and function, it also induces the intracellular accumulation of reactive oxygen species, resulting in membrane lipid peroxidation. In conclusion, these findings provide a theoretical foundation for the potential use of borneol in the food industry to prevent and control pathogenic fungal contamination.