Assessing the potential of four cathelicidins for the management of mouse candidiasis and Candida albicans biofilms.

Abstract

As the most common fungal pathogen of humans, severe drug resistance has emerged in the clinically isolated Candida albicans, which lead to the urgency to develop novel antifungal agents. Here, four our previously characterized cathelicidins (cathelicidin-BF, Pc-CATH1, Cc-CATH2, Cc-CATH3) were selected and their antifungal activities against C.albicans were evaluated invitro and invivo using amphotericin B and LL-37 as control. Results showed that all four cathelicidins could eradicate standard and clinically isolated C.albicans strains with most MIC values ranging from 1 to 16μg/ml, in less than 0.5h revealed by time-kill kinetic assay. Four peptides only exhibited slight hemolytic activity with most HC50>200μg/ml, and retained potent anti-C.albicans activity at salt concentrations below and beyond physiological level. In animal experiment, 50mg/kg administration of the four cathelicidins could significantly reduce the fungal counts in a murine oral candidiasis model induced by clinically isolated C.albicans. The antibiofilm activity of cathelicidin-BF, the most potent among the five peptides was evaluated, and result showed that cathelicidin-BF strongly inhibited C.albicans biofilm formation at 20μg/ml. Furthermore, cathelicidin-BF also exhibited potent anti-C.albicans activity in established biofilms as measured by metabolic and fluorescent viability assays. Structure-function analyses suggest that they mainly adopt an α-helical conformations, which enable them to act as a membrane-active molecule. Altogether, the four cathelicidins display great potential for antifungal agent development against candidiasis.