Antimicrobial Agents and Chemotherapy vol:58 issue:9 pages:5395-5404
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 human antimicrobial peptide LL-37. 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 these concentrations. 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 viability or functionality of different cell types involved in osseointegration of an implant, pointing to the potential of AS10 as a lead peptide for further development to coat implants.