The Antimicrobial Peptide Gad-1 Clears Pseudomonas aeruginosa Biofilms under Cystic Fibrosis Conditions

Chembiochem. 2021 May 4;22(9):1646-1655. doi: 10.1002/cbic.202000816. Epub 2021 Feb 24.

Abstract

Bacterial infections in cystic fibrosis (CF) patients are an emerging health issue and lead to a premature death. CF is a hereditary disease that creates a thick mucus in the lungs that is prone to bacterial biofilm formation, specifically Pseudomonas aeruginosa biofilms. These biofilms are very difficult to treat because many of them have antibiotic resistance that is worsened by the presence of extracellular DNA (eDNA). eDNA helps to stabilize biofilms and can bind antimicrobial compounds to lessen their effects. The metallo-antimicrobial peptide Gaduscidin-1 (Gad-1) eradicates established P. aeruginosa biofilms through a combination of modes of action that includes nuclease activity that can cleave eDNA in biofilms. In addition, Gad-1 exhibits synergistic activity when used with the antibiotics kanamycin and ciprofloxacin, thus making Gad-1 a new lead compound for the potential treatment of bacterial biofilms in CF patients.

Keywords: Pseudomonas aeruginosa; antibiofilm; antimicrobial; cystic fibrosis; nuclease activity.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • Antimicrobial Peptides / chemistry
  • Antimicrobial Peptides / pharmacology*
  • Biofilms / drug effects*
  • Cystic Fibrosis / microbiology
  • Cystic Fibrosis / pathology
  • DNA, Environmental / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Microbial Sensitivity Tests
  • Plasmids / metabolism
  • Pseudomonas aeruginosa / physiology*

Substances

  • Anti-Infective Agents
  • Antimicrobial Peptides
  • DNA, Environmental