Fungicidal activity of the human peptide hepcidin 20 alone or in combination with other antifungals against Candida glabrata isolates.
Candida glabrata infections are often difficult to eradicate due to the intrinsically low susceptibility to azoles of this species. In addition, C. glabrata has also been shown to be insensitive to several cationic peptides, which have been shown to be promising novel therapeutic candidates for the treatment of fungal infection. In this study, the in vitro fungicidal activity of the human cationic peptide hepcidin 20 (Hep-20) was evaluated against clinical isolates of C. glabrata with different levels of fluconazole susceptibility. Interestingly, all isolates were susceptible to Hep-20 (100-200 μg/ml) at pH 7.4, whereas the fungicidal effect of the peptide was higher (50 μg/ml) at acidic pH values. In addition, an increased antifungal activity was observed for Hep-20 with amphotericin B and a synergistic effect was demonstrated for the Hep-20/fluconazole and Hep-20/caspofungin combinations.
Dipartimento di Biologia, Università di Pisa, Via San Zeno, 37, 56127 Pisa, Italy. atavanti@biologia.unipi.it
Arianna
A
Tavanti
Giuseppantonio
G
Maisetta
Gaetano
G
Del Gaudio
Raffaele
R
Petruzzelli
Maurizio
M
Sanguinetti
Giovanna
G
Batoni
Sonia
S
Senesi
D000143:Acids / Q000737:chemistry; D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D041221:Candida glabrata / Q000187:drug effects*; D000077336:Caspofungin; D004357:Drug Synergism; D054714:Echinocandins / Q000494:pharmacology; D015725:Fluconazole / Q000494:pharmacology; D064451:Hepcidins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*
D000143:Acids; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D054714:Echinocandins; D064451:Hepcidins; D055666:Lipopeptides; D010446:Peptide Fragments; C542573:hepcidin (6-25), human; D000666:Amphotericin B; D015725:Fluconazole; D000077336:Caspofungin