Synthetic Human Lactoferrin Peptide hLF(1-11) Shows Antifungal Activity and Synergism with Fluconazole and Anidulafungin Towards Candida albicans and Various Non-Albicans Candida Species, Including Candidozyma auris.

INTRODUCTION: Candidozyma auris (Cz. auris) has emerged globally, and diseases caused by it are associated with a mortality rate of 30-72%. This yeast is often multidrug-resistant and challenging to treat. A synthetic peptide, consisting of 11 amino acids of human lactoferrin (hLF1-11), offers a new therapy that is active against Candida albicans, non-albicans Candida yeasts, as well as Cz. auris. The current study examined the susceptibility of clinically relevant Candida species to hLF(1-11) in vitro and investigated the synergistic interaction of this peptide with fluconazole (FLU) and anidulafungin (ANI). METHODS: Susceptibility of the yeasts to hLF(1-11) was tested with a microdilution method to determine minimum inhibitory concentrations (MICs). A total of 59 strains belonging to 16 species of Candida or Candidozyma were tested. The treatment cohort included 20 strains of Cz. auris originating from six different countries. RESULTS: Mean MIC values of all susceptible strains ranged from 16.66 ± 6.46 μg/mL to 45.83 ± 10.21 μg/mL. There were no statistical differences in the susceptibility of hLF(1-11) for Cz. auris across geographic origins. In the combinatory tests, drugs acting together, the fractional inhibitory concentration indexes [FIC] < 1.0, showed a synergistic or additive effect on the efficacy of FLU and ANI when used in combination with hLF(1-11). [FIC] indexes 1-2 were interpreted as intermediate. MIC values in combinatory use were 1-2 titer steps lower than when used alone. CONCLUSIONS: hLF(1-11) inhibits the growth of yeasts that belong to the genus Candida, including Cz. auris. The combinatory use may be further investigated to treat infections caused by resistant yeasts.