JAC Advance Access originally published online on October 5, 2006
Journal of Antimicrobial Chemotherapy 2006 58(5):950-959; doi:10.1093/jac/dkl382
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Fungicidal activity of five cathelicidin peptides against clinically isolated yeasts
1 Department of Biochemistry, Biophysics and Macromolecular Chemistry, University of Trieste 34127 Trieste, Italy 2 Department of Biomedical Sciences, University of Trieste Trieste, Italy 3 S.C. Microbiology, Immunology, Virology, Centro di Riferimento Oncologico IRCCS, Aviano (PN), Italy 4 Department of Public Medicine Sciences, UCO Hygiene and Preventive Medicine, University of Trieste IRCCS Burlo Garofolo, Trieste, Italy
Received 29 May 2006; returned 4 July 2006; revised 20 July 2006; accepted 17 August 2006
*Corresponding author. Tel: +39-040-558-3990; Fax: +39-040-558-3691; E-mail: scocchi{at}bbcm.units.it
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 µM, 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.
Keywords: antifungals , host defence , cathelicidin , clinical isolates , pathogenic fungi , innate immunity , immunocompromised patients
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