ACS Omega· 2026Q1
Plant Dehydrin-Derived, Lysine-Rich Peptides Show Both Antifungal Activity and Blood–Brain Barrier Penetration
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- 2026year
Short summary
Lysine-rich peptides derived from plant dehydrins, specifically ERD-A and its variants, demonstrate tunable antifungal activity against Candida albicans and Cryptococcus neoformans, with several variants showing 4-fold lower MIC values than the parent peptide. These peptides also exhibit high permeability across an in vitro blood-brain barrier model, exceeding that of a reference peptide.
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Key points
- Lysine-rich peptide ERD-A and its variants derived from plant dehydrins exhibit antifungal activity against Candida albicans and Cryptococcus neoformans.
- Sequence modifications, such as increased cationicity or tryptophan introduction, enhanced antifungal potency against C. neoformans, with some variants showing 4-fold lower MICs.
- ERD-A derived peptides demonstrated strong, time-dependent cell association with C. albicans (up to 98-99% positive cells after 16h).
- All ERD-A derived peptides showed higher in vitro blood-brain barrier (BBB) permeability than the reference peptide opiorphin.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract The plant-based, dehydrin-derived peptides represent an underexplored source of antifungal agents. In this study, we investigated the antifungal activity, cellular association, and blood–brain barrier (BBB) permeability of a lysine-rich peptide (ERD-A) derived from the Arabidopsis thaliana dehydrin ERD14, as well as its rationally designed sequence variants. The amino acid substitutions were engineered to modulate charge, aromatic residue content, and conformational flexibility. Antifungal activity was assessed against clinically relevant yeasts, including Candida albicans, Candidozyma auris, and Cryptococcus neoformans. The parental ERD-A peptide exhibited moderate activity against C. albicans and C. neoformans, while most variants showed species-dependent changes in potency. Increased cationicity or introduction of tryptophan residues enhanced activity against C. neoformans, with several variants displaying 4-fold lower MIC values than the parental peptide. In contrast, C. auris showed limited susceptibility to all tested variants. Fluorescence microscopy and flow cytometry demonstrated strong, time-dependent cell association of carboxyfluorescein-labeled ERD-A in C. albicans, reaching ∼98 to 99% positive cells after 16 h. BBB permeability was evaluated using an in vitro model of cocultured human brain endothelial cells with pericytes. All ERD-A-derived peptides exhibited higher permeability than that of the reference BBB-penetrating peptide opiorphin. The parental peptide showed high permeability, and selected variants retained or slightly improved this property. All these results demonstrate that ERD-A constitutes a tunable antifungal scaffold in which targeted sequence modifications modulate antifungal activity while preserving cell-penetrating and BBB-crossing properties. These features highlight ERD-A-derived peptides as candidates for multifunctional antifungal agents, particularly for central nervous system infections.
The authors' abstract, as published at the source. ACS Omega, 2026 · DOI ↗
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MicrobiologyImmunology and Microbiology