The antiproliferative peptide Ctn[15-34] is active against multidrug-resistant yeasts and Candida albicans and C. neoforms

Abstract

ims: Crotalicidin (Ctn), a cathelicidin-related antimicrobial peptide from theSouth American rattlesnake venom gland, and its C-terminal Ctn[15-34] fragment,have exhibited important activities against micro-organisms, trypanosomatidprotozoa and certain lines of tumour cells. Herein, the activity against clinicalstrains of fluconazole-resistant Candida albicans and of amphotericin B andfluconazole-resistant Cryptococcus neoformans was investigated.Methods and Results: Microdilution and luminescent cell viability tests wereused to evaluate and compare the susceptibility of pathogenic yeasts to thesepeptides. The time–kill curves of the most active Ctn[15-34] alone or incombination with fluconazole against drug-resistant yeasts were determined.Concomitantly, the fungicidal and/or fungistatic effects of Ctn[15-34] werevisualized by the spotting test. The peptides were active against all strains,including those resistant to antifungal agents. The association of fluconazolewith both Ctn and Ctn[15-34], although not synergic, was additive. Incontrast, such pattern was not observed for C. neoformans.Conclusions: Overall, Ctn and Ctn[15-34] are potential antifungal leadsdisplaying anti-yeast activities against clinical isolates endowed with drugresistance mechanisms.Significance and Impact of the Study: The effective peptide activity againstresistant strains of pathogenic yeasts demonstrates that crotalicidin-derivedpeptides are promising templates to develop new antifungal pharmaceuthicals