Fungicidal activity of five cathelicidin peptides against clinically isolated yeasts

• Published in: Journal of antimicrobial chemotherapy Vol. 58; no. 5; pp. 950 - 959
• Main Authors: Benincasa, Monica, Scocchi, Marco, Pacor, Sabrina, Tossi, Alessandro, Nobili, Donatella, Basaglia, Giancarlo, Busetti, Marina, Gennaro, Renato
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2006; Oxford Publishing Limited (England)
• Subjects: Amino Acid Sequence; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal Agents - pharmacokinetics; Antifungal Agents - pharmacology; antifungals; Antimicrobial Cationic Peptides - pharmacokinetics; Antimicrobial Cationic Peptides - pharmacology; Biological and medical sciences; Candida albicans; Candida albicans - drug effects; Candida albicans - isolation & purification; Candida albicans - metabolism; Candidiasis - microbiology; cathelicidin; Cattle; Cell Membrane Permeability - drug effects; Chemotherapy; clinical isolates; Cryptococcosis - microbiology; Cryptococcus neoformans; Cryptococcus neoformans - drug effects; Cryptococcus neoformans - isolation & purification; Cryptococcus neoformans - metabolism; Fungal infections; host defence; Humans; immunocompromised patients; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; innate immunity; Medical sciences; Microbial Sensitivity Tests; Molecular Sequence Data; pathogenic fungi; Peptides; Pharmacology; Pharmacology. Drug treatments; Swine; Yeast; Human; Immunopathology; Yeast; Peptides; Natural immunity; antifungals; clinical isolates; pathogenic fungi; Immune deficiency; Biological activity; Fungi; Pathogenicity; Cathelicidin; Antifungal agent; Immunosuppression; innate immunity; Pathogenic; host defence; immunocompromised patients; Clinical isolate; Thallophyta
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkl382

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.