Purpose:
To investigate the candidacidal activity of a novel
compound CF66I and attempt to elucidate its mode of
action.
Methods:
Minimal inhibition concentrations (MIC) and minimal
fungicidal concentrations (MFC) of CF66I for Candida
albicans were determined using serial broth dilution
method. Colony count assay, K+ release,
propidium iodide (PI) uptake and electron microscopy
were used to determine the manner in which CF66I exerts
its candidacidal effects.
Results:
MIC and MFC of CF66I were
determined to be 5.0 - 7.0 μg/ml and 14.0 - 18.0 μg/ml.
It showed strong candidacidal activity over a wide pH
range (4.0-7.4). The compound killed C. albicans within
30 s. It preferentially bound to the surface of C.
albicans via a specific interaction with β-1,6-glucan,
one of fungal cell wall components, and then affected
the normal structure of fungal cell wall and induced
cell wall thickening, which was confirmed by
transmission electron microscopy (TEM) CF66I also
exerted its candidacidal activity against cell membrane,
eventually induced K+ release from C.
albicans and PI uptake. Membrane-attacking ability was
also found via electron microscopy.
Conclusion:
These results suggest that
CF66I exerted its candidacidal activity on multiple
target sites on C. albicans, and may have considerable
potential for development of a new class of antifungal
agents.
Keywords:
Burkholderia cepacia, Candidacidal activity; CF66I;
Candida albicans; Mode of action