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Anti-Biofilm and Immunomodulatory Activities of Peptides That Inhibit Biofilms Formed by Pathogens Isolated from

César de la Fuente-Núñez1, Sarah C Mansour1, Zhejun Wang2

  • 1Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.

Antibiotics (Basel, Switzerland)
|July 30, 2015
PubMed

Insights

New anti-biofilm peptides show promise for treating chronic infections in cystic fibrosis (CF) patients. These peptides effectively combat bacterial biofilms and modulate immune responses, offering potential new therapies for CF lung disease.

Area of Science:

  • Microbiology
  • Biochemistry
  • Immunology

Background:

  • Cystic fibrosis (CF) patients are susceptible to chronic respiratory infections by Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) species.
  • Bacteria in CF lungs form biofilms, which are resistant to conventional antibiotics, necessitating novel therapeutic strategies.
  • Current treatments lack specific therapies targeting bacterial biofilms in CF.

Purpose of the Study:

  • To evaluate the anti-biofilm activity of peptide 1018 and its derivatives against key CF pathogens.
  • To assess the immunomodulatory effects and toxicity of these peptides on human immune cells.
  • To explore the potential of these peptides as novel therapeutics for CF-related biofilm infections and lung inflammation.

Main Methods:

  • Utilized in vitro biofilm models (plastic adherent, hydroxyapatite, flow cell) and microscopy (confocal, scanning electron).
  • Tested peptide 1018 and derivatives against clinical isolates of P. aeruginosa, B. cenocepacia, and methicillin-resistant Staphylococcus aureus (MRSA).
  • Assessed peptide immunomodulatory activity by measuring chemokine (MCP-1) and cytokine (TNF-α) production in human peripheral blood mononuclear cells (PBMCs) and evaluated cell toxicity.

Main Results:

  • Peptide 1018 effectively prevented biofilm formation, eradicated mature biofilms, and killed biofilms of P. aeruginosa and B. cenocepacia.
  • Peptide derivatives showed comparable or reduced activity against P. aeruginosa biofilms but enhanced activity against MRSA biofilms.
  • Some derivatives retained immunomodulatory properties, inducing MCP-1 and suppressing TNF-α production in PBMCs without causing toxicity.

Conclusions:

  • Peptide 1018 and its novel derivatives demonstrate significant anti-biofilm efficacy against CF-relevant pathogens.
  • These peptides possess immunomodulatory capabilities and low toxicity, suggesting therapeutic potential.
  • Peptide 1018 and its derivatives represent promising candidates for treating chronic biofilm infections and hyperinflammatory lung disease in cystic fibrosis.
Keywords:
anti-biofilmantibiotic-resistancecystic fibrosisimmunomodulationpeptides

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