Abstract / Summary
Biofilm-associated persister cells contribute to the recurrence and treatment failure of Candida albicans infections. Here, two Histatin 5-derived peptides (P1 and P2) and their silver(I)-coordinated derivatives (M1 and M2) were evaluated against a vaginal C. albicans clinical isolate, focusing on persister-derived secondary biofilms. Amphotericin B-surviving cells regenerated mature biofilms reaching approximately 6.5 log CFU/well after 7 days. At 320 µmol L−1, P1, P2, M1, and M2 reduced secondary-biofilm biomass by 68%, 63%, 77%, and 70%, respectively, while M1 and M2 decreased residual metabolic activity to approximately 19% and 18%. Metallopeptides strongly downregulated SAP1, SAP2, SAP6, and ECE1, whereas P1 and P2 slightly upregulated ECE1. Silver(I) coordination enhanced antifungal and antibiofilm activity but increased host toxicity, highlighting the need to optimize the activity–toxicity balance of these Histatin-derived scaffolds.