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Combinatory Use of hLF(1-11), a Synthetic Peptide Derived from Human Lactoferrin, and Fluconazole/Amphotericin B
Carlo P J M Brouwer1,2, Bart Theelen2,3, Youp van der Linden2
1CBMR Scientific Inc., Edmonton, AB T6J4V9, Canada.
Objective:
The increasing resistance of Malassezia yeasts against commonly used antifungal drugs dictates the need for novel antifungal compounds. Human lactoferrin-based peptides show a broad spectrum of antimicrobial activities. Various assays were performed to find the optimal growth conditions of the yeasts and to assess cell viability, using media with low lipid content to avoid peptide binding to medium components.
Methods:
In the current study, we tested the antimicrobial susceptibility of 30 strains of M. furfur that cover the known IGS1 genotypic variation.
Results:
hLF(1-11) inhibited the growth of all species tested, resulting in minimum inhibitory concentrations (MIC) values ranging from 12.5 to 100 μg/mL. In the combinatory tests, the majority of fractional inhibitory concentration indexes (FIC) for the tested strains of M. furfur were up to 1.0, showing that there is a synergistic or additive effect on the efficacy of the antifungal drugs when used in combination with hLF(1-11).
Conclusion:
Results showed that hLF(1-11) could be combined with fluconazole or amphotericin for the antimicrobial treatment of resistant strains, enhancing the potency of these antifungal drugs, resulting in an improved outcome for the patient.
Insights
Human lactoferrin peptide hLF(1-11) effectively combats resistant Malassezia furfur strains. Combining hLF(1-11) with existing antifungals enhances treatment efficacy against yeast infections.
Area of Science:
- Mycology
- Biochemistry
- Antimicrobial Research
Background:
- Growing resistance of Malassezia yeasts to conventional antifungal drugs necessitates new therapeutic agents.
- Human lactoferrin-derived peptides exhibit broad-spectrum antimicrobial properties.
- Optimizing yeast growth conditions and viability assays in low-lipid media is crucial for evaluating peptide efficacy.
Purpose of the Study:
- To evaluate the antimicrobial activity of human lactoferrin-derived peptide hLF(1-11) against Malassezia furfur.
- To assess the synergistic effects of hLF(1-11) in combination with established antifungal drugs.
Main Methods:
- Antimicrobial susceptibility testing of 30 Malassezia furfur strains with diverse IGS1 genotypes.
- Determination of minimum inhibitory concentrations (MIC) for hLF(1-11).
- Fractional inhibitory concentration index (FIC) calculations for drug combinations.
Main Results:
- hLF(1-11) demonstrated inhibitory activity against all tested Malassezia species, with MIC values between 12.5 and 100 μg/mL.
- Combinatory tests revealed synergistic or additive effects (FIC ≤ 1.0) for most Malassezia furfur strains when hLF(1-11) was combined with antifungal drugs.
- The peptide effectively inhibited yeast growth, indicating potential for enhanced antifungal therapies.
Conclusions:
- hLF(1-11) shows promise as a complementary agent in treating resistant Malassezia infections.
- Combination therapy with hLF(1-11) and standard antifungals like fluconazole or amphotericin can improve treatment outcomes.
- This approach enhances the potency of existing antifungal drugs against resistant yeast strains.
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