Objectives: To investigate the in vitro antifungal activity of the structurally different cathelicidin peptides
SMAP-29, BMAP-27, BMAP-28, protegrin-1 (PG-1) and indolicidin.
Methods: The in vitro antifungal and fungicidal activities of these antimicrobial peptides were
respectively assessed via MIC determinations and killing kinetics assays. The effects of the peptides
on membrane permeabilization and morphology were evaluated by flow cytometry, intracellular ATP
release measurements and scanning electron microscopy.
Results: All five peptides showed a potent but differential antifungal activity against more than 70
clinical isolates belonging to over 20 different species of pathogenic fungi; some of which are resistant
to amphotericin B and azoles. The MIC values of the peptides ranged between 0.5 and 32 mM, with PG-1
being the most effective and having the widest spectrum of activity. Filamentous fungi were instead
found to be scarcely susceptible to the action of these cathelicidin peptides. All these cathelicidins
rapidly killed Candida albicans and Cryptococcus neoformans cells in a dose- and time-dependent
manner. The rapid uptake of propidium iodide into treated cells and morphological alterations apparent
on their cellular surfaces suggest a killing mechanism based on membrane permeabilization and
damage.
Conclusions: This study indicates that these five structurally varied host defence peptides are all
endowed with the capacity to inactivate a number of fungal pathogens, irrespectively of their resistance
to antifungal drugs, and suggests they might be potentially useful leads for the development of novel
fungicidal agents.
