AUTHOR=Cools Tanne L. , Struyfs Caroline , Drijfhout Jan W. , Kucharíková Soňa , Lobo Romero Celia , Van Dijck Patrick , Ramada Marcelo H. S. , Bloch Carlos , Cammue Bruno P. A. , Thevissen Karin 

TITLE=A Linear 19-Mer Plant Defensin-Derived Peptide Acts Synergistically with Caspofungin against Candida albicans Biofilms

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.02051

DOI=10.3389/fmicb.2017.02051

ISSN=1664-302X

ABSTRACT=<p>Public health problems are associated with device-associated biofilm infections, with <italic>Candida albicans</italic> 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 <italic>C. albicans</italic> as HsLin06_18, a 19-mer peptide derived from the C-terminal part of HsAFP1. The [caspofungin + HsLin06_18] combination significantly reduced <italic>in vitro</italic> biofilm formation of <italic>Candida glabrata</italic> and <italic>C. albicans</italic> on catheters, as well as biofilm formation of a caspofungin-resistant <italic>C. albicans</italic> strain. The [caspofungin + HsLin06_18] combination was not cytotoxic and reduced biofilm formation of <italic>C. albicans in vivo</italic> 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.</p>