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

César De La Fuente-Núñez,Lucy Jiang,Ya Shen,Shauna Reckseidler-Zenteno,Elena Breidenstein,Zhejun Wang,Melissa Elliott,Fany Reffuveille,Robert Hancock,Markus Haapasalo,Sarah Mansour,David Speert

doi:10.3390/antibiotics3040509

César De La Fuente-Núñez, Lucy Jiang + Show 10 more

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https://doi.org/10.3390/antibiotics3040509

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Journal: Antibiotics	Publication Date: Oct 20, 2014
Citations: 81	License type: CC BY 4.0

Affiliation: University of British Columbia, Athabasca University

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.

Highlights

Bacteria form biofilms when growing on surfaces or air-liquid interfaces
P. aeruginosa and Burkholderia cenocepacia. The latter observation was surprising since planktonic B. cepacia complex strains are known to be completely resistant to the effects of cationic agents like polymyxin B and cationic antimicrobial peptides by virtue of their lack of a self-promoted uptake system across the outer membrane [32]
We extended our observations on the anti-biofilm activity vs. Burkholderia using a broad variety of B. cepacia complex species from cystic fibrosis (CF) patients and examined activity vs. a broad range of P. aeruginosa chronic pulmonary infection CF isolates, since these are known to form biofilms in the CF lung

Summary

Introduction

Bacteria form biofilms when growing on surfaces or air-liquid interfaces. Biofilms are structured aggregates of bacteria encased in a protective extracellular matrix that can contain polysaccharides, proteins, extracellular DNA, and lipids [1]. The switch from a free swimming, planktonic to an adherent biofilm lifestyle results in increased adaptive resistance to antimicrobial agents making biofilm-related infections inherently difficult to treat [1,2]. Apart from colonizing inert materials such as catheters and medical implants, bacterial biofilms are prevalent in chronic infections, such as those that develop in the lungs of cystic fibrosis (CF) patients [3,4]. CF patients rapidly acquire lifelong chronic respiratory infections that lead to hyper-inflammation and progressive destruction of lung function [5]

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