Covalently Immobilized Battacin Lipopeptide Gels with Activity against Bacterial Biofilms

Molecules. 2020 Dec 15;25(24):5945. doi: 10.3390/molecules25245945.

Abstract

Novel antibiotic treatments are in increasing demand to tackle life-threatening infections from bacterial pathogens. In this study, we report the use of a potent battacin lipopeptide as an antimicrobial gel to inhibit planktonic and mature biofilms of S. aureus and P. aeruginosa. The antimicrobial gels were made by covalently linking the N-terminal cysteine containing lipopeptide (GZ3.163) onto the polyethylene glycol polymer matrix and initiating gelation using thiol-ene click chemistry. The gels were prepared both in methanol and in water and were characterised using rheology, Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). Antibacterial and antibiofilm analyses revealed that the gels prepared in methanol have better antibacterial and antibiofilm activity. Additionally, a minimum peptide content of 0.5 wt% (relative to polymer content) is required to successfully inhibit the planktonic bacterial growth and disperse mature biofilms of P. aeruginosa and S. aureus. The antibacterial activity of these lipopeptide gels is mediated by a contact kill mechanism of action. The gels are non-haemolytic against mouse red blood cells and are non-cytotoxic against human dermal fibroblasts. Findings from this study show that battacin lipopeptide gels have the potential to be developed as novel topical antibacterial agents to combat skin infections, particularly caused by S. aureus.

Keywords: antimicrobial hydrogels; antimicrobial lipopeptides; bacterial biofilm inhibition; non haemolytic; non-cytotoxic.

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Gels
  • Immobilized Proteins / chemistry
  • Immobilized Proteins / pharmacology
  • Lipopeptides / chemistry*
  • Lipopeptides / pharmacology*
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / physiology
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / physiology

Substances

  • Anti-Bacterial Agents
  • Gels
  • Immobilized Proteins
  • Lipopeptides