A heptadeca amino acid peptide subunit of cathelicidin LL‐37 has previously unreported antifungal activity

Yeasts such as Candida albicans, albeit being ubiquitous members of the skin, oral and vaginal microbiome, can cause superficial to life‐threatening infections. Human cathelicidin LL‐37‐based peptides have antibacterial activity and yet, their antifungal activity remains to be thoroughly characterized. The aim of this study was to comprehensively investigate the activity of LL‐37‐based peptides against C. albicans. LL‐37 and its derivatives were tested for their ability to kill C. albicans planktonic cells in the presence of various biological matrices (serum, plasma, saliva and urine), that have been reported to inactivate peptides. The antibiofilm activity, resistance development and biocompatibility were investigated for the lead peptide. GK‐17, a 17 amino acid peptide, showed remarkable stability to fungal aspartyl proteases and rapidly killed planktonic C. albicans despite the presence of biological matrices. GK‐17 also inhibited adhesion to biotic and abiotic substrates, inhibited biofilm formation and eradicated preformed biofilms in the presence of biological matrices. Compared to nystatin, GK‐17 had a lower propensity to allow for resistance development by C. albicans. The peptide showed concentration‐dependent biocompatibility to red blood cells, with only 30% hemolysis even at 4× the fungicidal concentration. Taken together, GK‐17 is a novel antifungal peptide with promising effects against C. albicans.

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