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Updated: Jul 31, 2025
Quantifying the Antifungal Activity of Peptides Against Candida albicans
Published on: January 13, 2023
A heptadeca amino acid peptide subunit of cathelicidin LL-37 has previously unreported antifungal activity
Shanthini Kalimuthu1, Akhila Pudipeddi1, Grażyna Braś2
1Faculty of Dentistry, The University of Hong Kong, Sai Ying Pun, Hong Kong SAR.
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.
Insights
A novel peptide, GK-17, effectively combats Candida albicans, a common yeast causing infections. This peptide demonstrates potent antifungal activity, even in biological fluids, and inhibits biofilm formation, offering a promising therapeutic candidate.
Area of Science:
- Antimicrobial Peptides
- Medical Mycology
- Biochemistry
Background:
- Candida albicans is a prevalent yeast in the human microbiome, capable of causing opportunistic infections.
- Human cathelicidin LL-37 peptides possess known antibacterial properties, but their antifungal efficacy requires further investigation.
- Biological matrices like serum and saliva can reduce peptide activity, posing challenges for in vivo applications.
Purpose of the Study:
- To comprehensively evaluate the antifungal activity of LL-37-based peptides against Candida albicans.
- To assess the stability, efficacy, and safety profile of a lead peptide, GK-17, against C. albicans.
- To compare GK-17's performance against a standard antifungal agent, nystatin.
Main Methods:
- Testing LL-37 derivatives against planktonic C. albicans in various biological matrices.
- Evaluating GK-17's stability against fungal proteases and its activity in the presence of serum, plasma, saliva, and urine.
- Assessing GK-17's antibiofilm properties, including inhibition of adhesion, biofilm formation, and eradication of preformed biofilms.
- Investigating GK-17's potential for resistance development by C. albicans and its biocompatibility with red blood cells.
Main Results:
- GK-17 exhibited remarkable stability against fungal proteases and rapidly killed planktonic C. albicans, even in biological fluids.
- GK-17 effectively inhibited C. albicans adhesion and biofilm formation, and eradicated established biofilms in the presence of biological matrices.
- Compared to nystatin, GK-17 showed a lower propensity for inducing C. albicans resistance.
- GK-17 demonstrated concentration-dependent biocompatibility, with minimal hemolysis (30%) at four times the fungicidal concentration.
Conclusions:
- GK-17 is a potent and stable antifungal peptide with broad-spectrum activity against Candida albicans.
- GK-17 effectively combats planktonic cells and biofilms, even under challenging conditions with biological matrices.
- GK-17 presents a promising novel therapeutic candidate for treating C. albicans infections with a favorable safety profile.
