A Linear 19-Mer Plant Defensin-Derived Peptide Acts Synergistically with Caspofungin against Biofilms.

Public health problems are associated with device-associated biofilm infections, with being the major fungal pathogen. We previously identified potent antibiofilm combination treatment in which the antifungal plant defensin HsAFP1 is co-administered with caspofungin, the preferred antimycotic to treat such infections. In this study, we identified the smallest linear HsAFP1-derived peptide that acts synergistically with caspofungin or anidulafungin against as HsLin06_18, a 19-mer peptide derived from the C-terminal part of HsAFP1. The [caspofungin + HsLin06_18] combination significantly reduced biofilm formation of and on catheters, as well as biofilm formation of a caspofungin-resistant strain. The [caspofungin + HsLin06_18] combination was not cytotoxic and reduced biofilm formation of using a subcutaneous rat catheter model, as compared to control treatment. Mode of action research on the [caspofungin + HsLin06_18] combination pointed to caspofungin-facilitated HsLin06_18 internalization and immediate membrane permeabilization. All these findings point to broad-spectrum antibiofilm activity of a combination of HsLin06_18 and caspofungin.