• Echidnotoxin exhibits potent antifungal activity against drug-resistant strains, including Candida auris.
• The peptide disrupts fungal cell membranes and inhibits ergosterol synthesis, a novel dual mechanism.
• Synergistic effects with fluconazole enhance efficacy and reduce required dosages.
• In vivo studies show significant reduction in fungal burden and improved survival in a murine candidiasis model.