Vaginal
infections caused by Candida glabrata are difficult to eradicate due to this species' scarce susceptibility to
azoles. Previous studies have shown that the human cationic
peptide hepcidin 20 (Hep-20) exerts fungicidal activity in
sodium phosphate buffer against a panel of C. glabrata clinical isolates with different levels of susceptibility to
fluconazole. In addition, the activity of the
peptide was potentiated under acidic conditions, suggesting an application in the topical treatment of vaginal
infections. To investigate whether the
peptide activity could be maintained in biological fluids, in this study the antifungal activity of Hep-20 was evaluated by a killing assay in (i) a vaginal fluid simulant (VFS) and in (ii) human vaginal fluid (HVF) collected from three healthy donors. The results obtained indicated that the activity of the
peptide was maintained in VFS and HVF supplemented with
EDTA. Interestingly, the fungicidal activity of Hep-20 was enhanced in HVF compared to that observed in VFS, with a minimal fungicidal concentration of 25 μM for all donors. No cytotoxic effect on human cells was exerted by Hep-20 at concentrations ranging from 6.25 to 100 μM, as shown by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide
tetrazolium salt (XTT) reduction assay and
propidium iodide staining. A piece of indirect evidence of Hep-20 stability was also obtained from coincubation experiments of the
peptide with HVF at 37°C for 90 min and for 24 h. Collectively, these results indicate that this
peptide should be further studied as a novel therapeutic agent for the topical treatment of vaginal C. glabrata
infections.