Enhanced anti-Candida activity and mode of action of JII-R1, a jelleine-II peptide derivative of royal jelly origin
Candidiasis, the most frequent opportunistic mycoses, can range from a superficial disease to a life-threatening invasive candidiasis. Candida albicans remains the predominant etiological agent, but the incidence of candidiasis caused by Candida species with reduced susceptibility to the most common...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/410268 |
| Acceso en línea: | http://hdl.handle.net/10261/410268 https://api.elsevier.com/content/abstract/scopus_id/105020848966 |
| Access Level: | acceso abierto |
| Palabra clave: | Jelleines Antifungal activity Antimicrobial peptides Biofilms Candidiasis |
| Sumario: | Candidiasis, the most frequent opportunistic mycoses, can range from a superficial disease to a life-threatening invasive candidiasis. Candida albicans remains the predominant etiological agent, but the incidence of candidiasis caused by Candida species with reduced susceptibility to the most common antifungal drugs is increasing. Therefore, there is an urgent need to find novel antifungal compounds to treat candidiasis caused by these resistant pathogens. The aim of the present work was to evaluate the antifungal potential of jelleine-II, a short antimicrobial peptide present in the royal jelly of the bee Apis mellifera. This wild-type jelleine peptide and 14 derivatives were tested against five Candida species, including Candida parapsilosis, Candida glabrata (currently Nakaseomyces glabratus), Candida tropicalis, Candida krusei (currently Pichia kudriavzevii) and Candida auris (currently Candidozyma auris). First, the in vitro antifungal susceptibility was performed and the results showed an inhibitory and fungicidal activity. Model membrane permeabilization and hemolytic activity assays revealed the ability of the peptides to form stable structures as pores in membranes. The JII-R1 peptide, the most potent derivative of the wild-type jelleine-II peptide with the lowest (13.4 %) hemolytic activity, was selected for time-kill curve experiments and antifungal activity against both planktonic and sessile Candida cells. Therapeutic responses were also assessed in a Galleria mellonella candidiasis model. The JII-R1 derivative showed an improved anti-Candida activity and a better safety profile compared to the parent peptide. The treatment with the JII-R1 peptide, which was not toxic to larvae, was effective in protecting larvae during Candida infection. In conclusion, this is the first report describing the antifungal activity of the JII-R1 peptide, a derivative of jelleine-II peptide, against Candida and its biofilms. The JII-R1 derivative, due to its small size, low toxicity and good anti-Candida activity, is a promising template for the development of new therapeutic alternatives. |
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