Derivatives of the Mouse Cathelicidin-Related Antimicrobial Peptide (CRAMP) Inhibit Fungal and Bacterial Biofilm Formation |
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| Authors: | Katrijn De Brucker Nicolas Delattin Stijn Robijns Hans Steenackers Natalie Verstraeten Bart Landuyt Walter Luyten Liliane Schoofs Barbara Dovgan Mirjam Fr?hlich Jan Michiels Jos Vanderleyden Bruno P. A. Cammue Karin Thevissen |
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| Affiliation: | aCentre for Microbial and Plant Genetics, CMPG, KU Leuven, Leuven, Belgium;bAnimal Physiology and Neurobiology Section, KU Leuven, Leuven, Belgium;cDepartment of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium;dEducell, Trzin, Slovenia;eDepartment of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, Ljubljana, Slovenia;fDepartment of Plant Systems Biology, VIB, Ghent, Belgium |
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| Abstract: | We identified a 26-amino-acid truncated form of the 34-amino-acid cathelicidin-related antimicrobial peptide (CRAMP) in the islets of Langerhans of the murine pancreas. This peptide, P318, shares 67% identity with the LL-37 human antimicrobial peptide. As LL-37 displays antimicrobial and antibiofilm activity, we tested antifungal and antibiofilm activity of P318 against the fungal pathogen Candida albicans. P318 shows biofilm-specific activity as it inhibits C. albicans biofilm formation at 0.15 μM without affecting planktonic survival at that concentration. Next, we tested the C. albicans biofilm-inhibitory activity of a series of truncated and alanine-substituted derivatives of P318. Based on the biofilm-inhibitory activity of these derivatives and the length of the peptides, we decided to synthesize the shortened alanine-substituted peptide at position 10 (AS10; KLKKIAQKIKNFFQKLVP). AS10 inhibited C. albicans biofilm formation at 0.22 μM and acted synergistically with amphotericin B and caspofungin against mature biofilms. AS10 also inhibited biofilm formation of different bacteria as well as of fungi and bacteria in a mixed biofilm. In addition, AS10 does not affect the viability or functionality of different cell types involved in osseointegration of an implant, pointing to the potential of AS10 for further development as a lead peptide to coat implants. |
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