Enhancement of the antifungal activity against candida of jelleine-ii, an antimicrobial peptide from the royal jelly

Abstract

EN: Candidiasis, the most frequent opportunistic fungal infections, can range from a superficial diseaseto a life-threatening invasive candidiasis. Candida albicans remains the predominant aetiological agent,but the incidence of candidiasis caused by Candida species with reduced susceptibility to some of thecommonly employed antifungal drugs is increasing. Therefore, there is an urgent need to find novelantifungal compounds to face these resistant pathogens. The jelleines are a family of four shortantimicrobial peptides, present in the royal jelly of the bee Apis mellifera, that have been reported topossess antimicrobial activity against gram-positive and gram-negative bacteria, as well as againstCandida. The jelleine-I peptide has hoarded the focus among the four peptides, but the jelleine-II showeda comparable antimicrobial effect in their initial characterisation.Therefore, this Thesis work consisted in the characterisation and evaluation of the antifungal efficacy ofthe jelleine-II peptide and some derivatives against Candida species, including C. albicans, Candidaglabrata, Candida parapsilosis, Candida krusei and Candida auris. The sequence of the wild-typejelleine-II was altered by amino acid substitutions by following various approaches. Alanine scanningwas performed to determine the importance of each amino acid in the sequence of the jelleine-II for theantifungal activity of the peptide. Derivatives with arginine and/or tryptophan residues were tested withthe aim to obtain a derivative with enhanced antifungal activity against the aforementioned Candidaspecies.The evaluation of the antifungal efficacy via in vitro and in vivo assays led to the selection of a derivativeof the wild-type jelleine-II peptide, the JII-R1 peptide, which showed an improved antifungal activity andsafety profile in comparison to the parent peptide. The jelleine-II peptide and some of its derivativesexerted antifungal activity against both planktonic and sessile cells of Candida. As a conclusion, thosepeptides, especially the JII-R1 derivative, are promising antifungal molecules because of their lowtoxicity and activity against Candida species.