Combinatory Use of hLF(1-11), a Synthetic Peptide Derived from Human Lactoferrin, and Fluconazole/Amphotericin B against Malassezia furfur Reveals a Synergistic/Additive Antifungal Effect

Author:

Brouwer Carlo P. J. M.12,Theelen Bart23ORCID,van der Linden Youp2,Sarink Nick2,Rahman Mahfuzur1,Alwasel Saleh4,Cafarchia Claudia5ORCID,Welling Mick M.6ORCID,Boekhout Teun24

Affiliation:

1. CBMR Scientific Inc., Edmonton, AB T6J4V9, Canada

2. Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands

3. Division of Pediatric Infectious Diseases, University of Minnesota Medical School, Minneapolis, MN 55455, USA

4. College of Sciences, King Saud University, Riyadh 11451, Saudi Arabia

5. Dipartimento di Medicina Veterinaria, Università degli Studi “Aldo Moro”, 70121 Bari, Italy

6. Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

Abstract

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.

Funder

King Saud University, Saudi Arabia

Publisher

MDPI AG

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