title: Derivatives of the mouse cathelicidin-related antimicrobial peptide (CRAMP) inhibit fungal and bacterial biofilm formation.
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.
authors: Centre for Microbial and Plant Genetics, CMPG, KU Leuven, Leuven, Belgium.
authors: Katrijn
authors: K
authors: De Brucker
authors: Centre for Microbial and Plant Genetics, CMPG, KU Leuven, Leuven, Belgium.
authors: Nicolas
authors: N
authors: Delattin
authors: Centre for Microbial and Plant Genetics, CMPG, KU Leuven, Leuven, Belgium.
authors: Stijn
authors: S
authors: Robijns
authors: Centre for Microbial and Plant Genetics, CMPG, KU Leuven, Leuven, Belgium.
authors: Hans
authors: H
authors: Steenackers
authors: Centre for Microbial and Plant Genetics, CMPG, KU Leuven, Leuven, Belgium.
authors: Natalie
authors: N
authors: Verstraeten
authors: Animal Physiology and Neurobiology Section, KU Leuven, Leuven, Belgium.
authors: Bart
authors: B
authors: Landuyt
authors: Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors: Walter
authors: W
authors: Luyten
authors: Animal Physiology and Neurobiology Section, KU Leuven, Leuven, Belgium.
authors: Liliane
authors: L
authors: Schoofs
authors: Educell, Trzin, Slovenia.
authors: Barbara
authors: B
authors: Dovgan
authors: Educell, Trzin, Slovenia Department of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, Ljubljana, Slovenia.
authors: Mirjam
authors: M
authors: Fröhlich
authors: Centre for Microbial and Plant Genetics, CMPG, KU Leuven, Leuven, Belgium.
authors: Jan
authors: J
authors: Michiels
authors: Centre for Microbial and Plant Genetics, CMPG, KU Leuven, Leuven, Belgium.
authors: Jos
authors: J
authors: Vanderleyden
authors: Centre for Microbial and Plant Genetics, CMPG, KU Leuven, Leuven, Belgium Department of Plant Systems Biology, VIB, Ghent, Belgium bruno.cammue@biw.kuleuven.be.
authors: Bruno P A
authors: BP
authors: Cammue
authors: Centre for Microbial and Plant Genetics, CMPG, KU Leuven, Leuven, Belgium.
authors: Karin
authors: K
authors: Thevissen
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects*; D000077336:Caspofungin; D054804:Cathelicidins / Q000494:pharmacology*; D054714:Echinocandins / Q000494:pharmacology; D006801:Humans; D055666:Lipopeptides; D051379:Mice; D008826:Microbial Sensitivity Tests / Q000379:methods; D010933:Plankton / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D054714:Echinocandins; D055666:Lipopeptides; D000666:Amphotericin B; D000077336:Caspofungin