Author:

Abstract:

Public health problems are frequently associated with device-associated biofilm infections, with Candida albicans being the major fungal pathogen in this respect. We identified potent antibiofilm combination treatment in which caspofungin, the preferred antimycotic to treat such infections, is co-administered with a peptide, either a native antifungal plant defensin such as HsAFP1 isolated from the plant Heuchera sanguinea or linear HsAFP1-derived peptides. In this regard, we identified the 19-mer peptide HsLin06_18, which is the smallest linear HsAFP1-derived peptide that can still increase caspofungin’s but also anidulafungin’s antibiofilm activity. We found that a combination of caspofungin and HsLin06_18 significantly reduced survival of C. glabrata and C. albicans biofilms grown on catheters, which was confirmed in a subcutaneous rat catheter model. Mode of action research on the caspofungin-HsLin06_18 combination points to uptake of HsLin06_18 upon treatment with subinhibitory caspofungin doses, resulting in immediate membrane permeabilization. All these findings point to broad-spectrum antibiofilm activity of a combination of HsLin06_18 and caspofungin and to its clinical potential to treat fungal biofilm-based infections.