Fungicidal activity of five cathelicidin peptides against clinically isolated yeasts

Monica Benincasa, Marco Scocchi, Sabrina Pacor, Alessandro Tossi, Donatella Nobili, Giancarlo Basaglia, Marina Busetti, Renato Gennaro

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)950-959
Number of pages10
JournalJournal of Antimicrobial Chemotherapy
Volume58
Issue number5
DOIs
Publication statusPublished - 2006

Fingerprint

Yeasts
Peptides
Fungal Drug Resistance
Cathelicidins
Fungi
Azoles
Cryptococcus neoformans
Membranes
Propidium
Amphotericin B
CAP18 lipopolysaccharide-binding protein
Candida albicans
Electron Scanning Microscopy
Flow Cytometry
Adenosine Triphosphate
In Vitro Techniques
protegrin-1

Keywords

  • Antifungals
  • Cathelicidin
  • Clinical isolates
  • Host defence
  • Immunocompromised patients
  • Innate immunity
  • Pathogenic fungi

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases
  • Pharmacology (medical)
  • Pharmacology

Cite this

Benincasa, M., Scocchi, M., Pacor, S., Tossi, A., Nobili, D., Basaglia, G., ... Gennaro, R. (2006). Fungicidal activity of five cathelicidin peptides against clinically isolated yeasts. Journal of Antimicrobial Chemotherapy, 58(5), 950-959. https://doi.org/10.1093/jac/dkl382

Fungicidal activity of five cathelicidin peptides against clinically isolated yeasts. / Benincasa, Monica; Scocchi, Marco; Pacor, Sabrina; Tossi, Alessandro; Nobili, Donatella; Basaglia, Giancarlo; Busetti, Marina; Gennaro, Renato.

In: Journal of Antimicrobial Chemotherapy, Vol. 58, No. 5, 2006, p. 950-959.

Research output: Contribution to journalArticle

Benincasa, M, Scocchi, M, Pacor, S, Tossi, A, Nobili, D, Basaglia, G, Busetti, M & Gennaro, R 2006, 'Fungicidal activity of five cathelicidin peptides against clinically isolated yeasts', Journal of Antimicrobial Chemotherapy, vol. 58, no. 5, pp. 950-959. https://doi.org/10.1093/jac/dkl382
Benincasa, Monica ; Scocchi, Marco ; Pacor, Sabrina ; Tossi, Alessandro ; Nobili, Donatella ; Basaglia, Giancarlo ; Busetti, Marina ; Gennaro, Renato. / Fungicidal activity of five cathelicidin peptides against clinically isolated yeasts. In: Journal of Antimicrobial Chemotherapy. 2006 ; Vol. 58, No. 5. pp. 950-959.
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