title: Anti-Biofilm and Immunomodulatory Activities of Peptides That Inhibit Biofilms Formed by Pathogens Isolated from Cystic Fibrosis Patients.
abstract: Cystic fibrosis (CF) patients often acquire chronic respiratory tract infections due to Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) species. In the CF lung, these bacteria grow as multicellular aggregates termed biofilms. Biofilms demonstrate increased (adaptive) resistance to conventional antibiotics, and there are currently no available biofilm-specific therapies. Using plastic adherent, hydroxyapatite and flow cell biofilm models coupled with confocal and scanning electron microscopy, it was demonstrated that an anti-biofilm peptide 1018 prevented biofilm formation, eradicated mature biofilms and killed biofilms formed by a wide range of P. aeruginosa and B. cenocepacia clinical isolates. New peptide derivatives were designed that, compared to their parent peptide 1018, showed similar or decreased anti-biofilm activity against P. aeruginosa biofilms, but increased activity against biofilms formed by the Gram-positive bacterium methicillin resistant Staphylococcus aureus. In addition, some of these new peptide derivatives retained the immunomodulatory activity of 1018 since they induced the production of the chemokine monocyte chemotactic protein-1 (MCP-1) and suppressed lipopolysaccharide-mediated tumor necrosis factor-α (TNF-α) production by human peripheral blood mononuclear cells (PBMC) and were non-toxic towards these cells. Peptide 1018 and its derivatives provide promising leads for the treatment of chronic biofilm infections and hyperinflammatory lung disease in CF patients.
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: César
authors.initials: C
authors.lastname: de la Fuente-Núñez
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Mansour
authors.affiliation: Division of Endodontics, Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Zhejun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Lucy
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Elena B M
authors.initials: EB
authors.lastname: Breidenstein
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Melissa
authors.initials: M
authors.lastname: Elliott
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Fany
authors.initials: F
authors.lastname: Reffuveille
authors.affiliation: Department of Pediatrics, University of British Columbia, Vancouver, BC, V6H 3V4, Canada.
authors.forename: David P
authors.initials: DP
authors.lastname: Speert
authors.affiliation: Athabasca University, Athabasca, AB, T9S 3A3, Canada.
authors.forename: Shauna L
authors.initials: SL
authors.lastname: Reckseidler-Zenteno
authors.affiliation: Division of Endodontics, Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Ya
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Division of Endodontics, Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Markus
authors.initials: M
authors.lastname: Haapasalo
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
keywords: anti-biofilm; antibiotic-resistance; cystic fibrosis; immunomodulation; peptides