How do lipopeptides interact with the model fungal membrane?

Candida albicans is the predominant cause of both mucosal and systemic fungal infections, accounting for approximately 70% of cases worldwide. To combat such infections, several classes of antifungal drugs have been developed, including amphotericin B (AmpB), triazoles, and echinocandins. These agents act through distinct mechanisms - binding to ergosterol, inhibiting ergosterol biosynthesis, or inactivating glucan synthase. However, the emergence of drug resistance, mediated by reduction in membrane uptake, target site modifications, and overexpression of drug targets, has significantly diminished the efficacy of conventional therapies. To address this dilemma, for instance, the antimicrobial peptide (AMP) GIK shows good antimicrobial properties in treating drug-resistant fungi compared to conventional drugs. Lipopeptide, with a shorter amino acid sequence and comparable properties, such as rapid antifungal actions and broad-spectrum activities, is a more promising candidate antifungal drug to be utilised clinically. To unravel how designed lipopeptides bind with model fungal membrane, neutron reflection experiment is proposed, adding structural details to the characterizations undertaken by CD, Zeta-potential and QCM-D measurements. The NR results will teach us how to further improve antifungal lipopeptides.