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Peer-reviewedCC BY-NCInfection and drug resistance

The Plant-Derived Peptide Hyde C1 Exhibits Membrane-Associated Antifungal Activity and Protects Against Systemic Candida albicans Infection.

  1. 1Department of Biology, QaS.C., Islamic Azad University, Qaemshahr, Iran.
  2. 2Department of Mycology, Pasteur Institute of Iran, Tehran, Iran.
  3. 3Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

Purpose

Invasive candidiasis and increasing antifungal resistance underscore the need for alternative therapeutic approaches. Antimicrobial peptides are of interest because of their antifungal activity and potential membrane-associated effects. This study evaluated Hyde C1, a plant-derived antimicrobial peptide from Cichorium intybus, for antifungal activity against Candida albicans and examined whether its effects were associated with fungal membrane-associated effects.Methods

Antifungal activity against C. albicans ATCC 10231 was assessed using minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and time-kill assays. Membrane permeability and cellular morphology were examined by propidium iodide uptake, transmission electron microscopy, and scanning electron microscopy. Molecular docking assessed the predicted interaction of Hyde C1 with a model yeast membrane environment. Therapeutic effects were evaluated in a cyclophosphamide-induced murine model of systemic candidiasis by assessing survival, kidney fungal burden, and renal histopathology.Results

Hyde C1 showed antifungal activity with an MIC of 16 μg/mL and an MFC of 32 μg/mL. Time-kill analysis showed concentration- and time-dependent reductions in fungal viability. Hyde C1 increased propidium iodide uptake and produced ultrastructural and surface morphological alterations in fungal cells, findings consistent with membrane-associated antifungal activity. Docking analysis indicated a favorable predicted interaction with the model yeast membrane environment. In vivo, Hyde C1 treatment improved survival, reduced kidney fungal burden, and was associated with less pronounced infection-related renal histopathological changes than in untreated infected mice.Discussion

Hyde C1 exhibited antifungal activity against C. albicans and protective effects in a murine model of systemic candidiasis. The combined in vitro, computational, and in vivo findings support further investigation of this plant-derived peptide as an antifungal therapeutic candidate with membrane-associated activity. Additional studies are required to define its molecular mechanism, pharmacokinetic properties, safety profile, and reproducibility across broader experimental models.

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BibTeX
@article{alamshiri2026plantderived,
  title = {{The Plant-Derived Peptide Hyde C1 Exhibits Membrane-Associated Antifungal Activity and Protects Against Systemic Candida albicans Infection.}},
  author = {Atefeh Nikzad Alamshiri and Sima Sadat Seyedjavadi and Fatemeh Peyravii Ghadikolaii and Mehdi Goudarzi},
  journal = {Infection and drug resistance},
  year = {2026},
  month = oct,
  doi = {10.2147/idr.s647734},
  url = {https://europepmc.org/article/MED/42974464},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - The Plant-Derived Peptide Hyde C1 Exhibits Membrane-Associated Antifungal Activity and Protects Against Systemic Candida albicans Infection.
AU  - Atefeh Nikzad Alamshiri
AU  - Sima Sadat Seyedjavadi
AU  - Fatemeh Peyravii Ghadikolaii
AU  - Mehdi Goudarzi
PY  - 2026
DA  - 2026/10/29
JO  - Infection and drug resistance
DO  - 10.2147/idr.s647734
UR  - https://europepmc.org/article/MED/42974464
AB  - Purpose  Invasive candidiasis and increasing antifungal resistance underscore the need for alternative therapeutic approaches. Antimicrobial peptides are of interest because of their antifungal activity and potential membrane-associated effects. This study evaluated Hyde C1, a plant-derived antimicrobial peptide from Cichorium intybus, for antifungal activity against Candida albicans and examined whether its effects were associated with fungal membrane-associated effects.Methods  Antifungal activity against C. albicans ATCC 10231 was assessed using minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and time-kill assays. Membrane permeability and cellular morphology were examined by propidium iodide uptake, transmission electron microscopy, and scanning electron microscopy. Molecular docking assessed the predicted interaction of Hyde C1 with a model yeast membrane environment. Therapeutic effects were evaluated in a cyclophosphamide-induced murine model of systemic candidiasis by assessing survival, kidney fungal burden, and renal histopathology.Results  Hyde C1 showed antifungal activity with an MIC of 16 μg/mL and an MFC of 32 μg/mL. Time-kill analysis showed concentration- and time-dependent reductions in fungal viability. Hyde C1 increased propidium iodide uptake and produced ultrastructural and surface morphological alterations in fungal cells, findings consistent with membrane-associated antifungal activity. Docking analysis indicated a favorable predicted interaction with the model yeast membrane environment. In vivo, Hyde C1 treatment improved survival, reduced kidney fungal burden, and was associated with less pronounced infection-related renal histopathological changes than in untreated infected mice.Discussion  Hyde C1 exhibited antifungal activity against C. albicans and protective effects in a murine model of systemic candidiasis. The combined in vitro, computational, and in vivo findings support further investigation of this plant-derived peptide as an antifungal therapeutic candidate with membrane-associated activity. Additional studies are required to define its molecular mechanism, pharmacokinetic properties, safety profile, and reproducibility across broader experimental models.
SN  - 1178-6973
ER  -