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

Abstract

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.

Secreted Aspartic Proteinases: Key Factors in Candida Infections and Host-Pathogen Interactions

“…Although its antimicrobial properties were described several years ago, it was only recently demonstrated that, like His5, the P-133 peptide can be cleaved into four shorter fragments with the participation of Saps [133]. Furthermore, the degradation of other truncated and derivative LL-37 peptides with antifungal properties has also been demonstrated by Saps [134]; some of them, including GK-17 peptide characterized in detail, showed less susceptibility to this proteolysis, especially Sap4 and Sap6-dependent [134]. Furthermore, there are also other defense proteins produced by the host that may be degraded by aspartic proteases, including salivary lactoferrin, lactoperoxidase, cathepsin D, α2-macroglobulin, etc.…”

Candida albicans Biofilm-Derived Extracellular Vesicles Are Involved in the Tolerance to Caspofungin, Biofilm Detachment, and Fungal Proteolytic Activity

“…Kininogen-derived peptide NAT26 with the amino acid sequence of NATFYFKID-NVKKARVQVVAGKKYFI was purchased from Lipopharm (Zblewo, Poland). Samples for peptide degradation in the presence of C. albicans EVs were prepared and analyzed similarly as described previously [39,40] with some modifications. Briefly, a 100 µL mixture of NAT26 peptide (at a final concentration of 10 µM) and 4 × 10 9 EVs was prepared in 20 mM phosphate buffer, pH 7.0, in Eppendorf tubes and incubated for 24 h at 37 • C. The peptide incubated only in the buffer served as a control.…”