Bioprospecting of Curcuma longa rhizomes reveals a 2.5 kDa antifungal peptide with potent anti-Candida albicans activity and synergistic interaction with nystatin.

Bioactive peptides from plant sources are promising alternatives to conventional antifungal therapies. Here, we report the isolation and partial characterisation of a low-molecular-weight antifungal peptide (∼2.5 kDa) from Curcuma longa rhizomes. Bioactivity-guided purification yielded a fraction with potent activity against Candida albicans (MIC = 0.7 μg/mL). In silico analysis identified candidate peptides, including fragments from curcumin synthase 1, consistent with the observed mass.1³C NMR revealed signals compatible with carbon environments associated with residues such as tryptophan and serine, typical of membrane-active peptides. Strong synergistic interactions were observed with nystatin and fluconazole (FIC indices of 0.11 and 0.30, respectively). Ultrastructural analyses (SEM/TEM) showed cell wall disruption and cytoplasmic disorganisation, supporting a membrane-targeting mechanism. The peptide also inhibited germ-tube formation at 2 x MIC. These findings highlight a promising plant-derived peptide for antifungal combination therapy.