Titanium surfaces immobilized with the major antimicrobial fragment FK-16 of human cathelicidin LL-37 are potent against multiple antibiotic-resistant bacteria

Biofouling. 2017 Aug;33(7):544-555. doi: 10.1080/08927014.2017.1332186. Epub 2017 Jul 4.

Abstract

Infections on implanted medical devices are a challenging problem, especially when bacteria form difficult-to-treat biofilms. Antimicrobial peptides are considered to be a solution due to their potency against antibiotic-resistant superbugs. Previously, the authors' laboratory demonstrated the prevention of staphylococcal biofilm formation in an animal catheter model by injecting merecidin (formerly known as 17BIPHE2), a peptide engineered based on the only human cathelicidin. This study documents an alternative solution via covalent immobilization of FK-16, amino acid sequence FKRIVQRIKDFLRNLV-amide, which corresponds to the major antimicrobial region (residues 17-32) of LL-37. FK-16 is superior to the longer peptide LL-37 in terms of synthesis cost and the shorter peptide KR-12 in terms of activity spectrum. Indeed, the FK16-coated titanium surface showed a broad-spectrum activity against the ESKAPE pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. It also demonstrated anti-adhesion and biofilm inhibition capabilities against both S. aureus and E. coli.

Keywords: Biofilms; ESKAPE pathogens; FK-16; LL-37; peptide immobilization; titanium.

MeSH terms

  • Acinetobacter baumannii / drug effects
  • Amino Acid Sequence
  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / toxicity
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology*
  • Antimicrobial Cationic Peptides / toxicity
  • Bacterial Adhesion / drug effects
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Cathelicidins
  • Catheters / microbiology
  • Cell Line
  • Cell Survival / drug effects
  • Erythrocytes / drug effects
  • Escherichia coli / drug effects
  • Hemolysis / drug effects
  • Humans
  • Keratinocytes / drug effects
  • Microbial Sensitivity Tests
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Peptide Fragments / toxicity
  • Pseudomonas aeruginosa / drug effects
  • Staphylococcus aureus / drug effects
  • Surface Properties
  • Titanium / chemistry*

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Peptide Fragments
  • Titanium
  • Cathelicidins