Fungicidal activity of five cathelicidin peptides against clinically isolated yeasts.
OBJECTIVE
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 microM, 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.
Benincasa
Monica
M
Department of Biochemistry, Biophysics and Macromolecular Chemistry, University of Trieste, 34127 Trieste, Italy.
Scocchi
Marco
M
Pacor
Sabrina
S
Tossi
Alessandro
A
Nobili
Donatella
D
Basaglia
Giancarlo
G
Busetti
Marina
M
Gennaro
Renato
R
D000595:Amino Acid Sequence; D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D002177:Candidiasis / Q000382:microbiology; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D003453:Cryptococcosis / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D013552:Swine; D054804:Cathelicidins
D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins