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Updated: Jun 6, 2026
Quantifying the Antifungal Activity of Peptides Against Candida albicans
Published on: January 13, 2023
Fungicidal activity of human lactoferrin-derived peptides based on the antimicrobial αβ region
N Kondori1, L Baltzer, G T Dolphin
1Department of Infectious Diseases/Clinical Bacteriology, University of Gothenburg, Guldhedsgatan 10, S-413 46 Gothenburg, Sweden.
Abstract:
Owing to the increasing number of infections in hospitalised patients caused by resistant strains of fungi, there is a need to develop new therapeutic agents for these infections. Naturally occurring antimicrobial peptides may constitute models for developing such agents. A modified peptide sequence (CFQWKRAMRKVR; HLopt2) based on amino acid residues 20-31 of the N-terminal end of human lactoferrin (hLF) as well as a double-sized human lactoferricin-like peptide (amino acid residues 16-40; HLBD1) were investigated for their antifungal activities in vitro and in vivo. By in vitro assay, HLopt2 was fungicidal at concentrations of 12.5-25 μg/mL against Cryptococcus neoformans, Candida albicans, Candida krusei, Candida kefyr and Candida parapsilosis, but not against Candida glabrata. HLopt2 was demonstrated to have ≥ 16-fold greater killing activity than HLBD1. By inducing some helical formation caused by lactam bridges or by extending the assay time (from 2h to 20 h), HLBD1 became almost comparable with HLopt2 in its fungicidal activity. Killing of C. albicans yeast cells by HLopt2 was rapid and was accompanied by cytoplasmic and mitochondrial membrane permeabilisation as well as formation of deep pits on the yeast cell surface. In a murine C. albicans skin infection model, atopic treatment with the peptides resulted in significantly reduced yields of Candida from the infected skin areas. The antifungal activities of HLopt2 in vitro and in vivo suggest possible potential as a therapeutic agent against most Candida spp. and C. neoformans. The greatly improved antifungal effect of the lactam-modified HLBD1 indicates the importance of amphipathic helix formation for lethal activity.
Insights
New antimicrobial peptides derived from human lactoferrin show potent antifungal activity against resistant fungal strains like Candida and Cryptococcus neoformans. These peptides demonstrate potential as novel therapeutic agents for treating challenging hospital-acquired fungal infections.
Area of Science:
- Microbiology
- Biochemistry
- Pharmacology
Background:
- Rising incidence of drug-resistant fungal infections in hospitalized patients necessitates novel therapeutic strategies.
- Naturally occurring antimicrobial peptides offer promising models for developing new antifungal agents.
- Human lactoferrin-derived peptides are being explored for their potential antimicrobial properties.
Purpose of the Study:
- To investigate the in vitro and in vivo antifungal activities of two modified human lactoferrin-derived peptides, HLopt2 and HLBD1.
- To compare the efficacy of HLopt2 and HLBD1 against various pathogenic fungi, including Candida species and Cryptococcus neoformans.
- To elucidate the mechanism of action of these peptides against fungal cells.
Main Methods:
- Synthesis and modification of peptide sequences based on human lactoferrin.
- In vitro antifungal assays to determine minimum fungicidal concentrations against a panel of fungi.
- In vivo efficacy testing using a murine model of Candida albicans skin infection.
- Microscopic analysis to observe peptide-induced damage to fungal cells.
Main Results:
- HLopt2 exhibited potent fungicidal activity against Cryptococcus neoformans and most Candida species at low concentrations (12.5-25 μg/mL), but not against Candida glabrata.
- HLopt2 demonstrated significantly greater killing activity (≥ 16-fold) compared to HLBD1.
- HLBD1's antifungal activity approached that of HLopt2 when modified with lactam bridges or when assay time was extended.
- In vivo studies showed that topical application of peptides significantly reduced fungal load in infected skin areas.
- Peptide-induced cell death involved cytoplasmic and mitochondrial membrane permeabilization and surface pitting.
Conclusions:
- HLopt2 shows significant potential as a therapeutic agent against common fungal pathogens like Candida spp. and Cryptococcus neoformans.
- The study highlights the importance of amphipathic helix formation for the potent antifungal activity of these peptides.
- Modified human lactoferrin-derived peptides represent a promising avenue for developing new treatments against resistant fungal infections.
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