Activity of a novel antimicrobial peptide against Pseudomonas aeruginosa biofilms

Abstract With the increasing recognition of biofilms in human disease, the development of novel antimicrobial therapies is of critical importance. For example, in patients with cystic fibrosis (CF), the acquisition of host-adapted, chronic Pseudomonas aeruginosa infection is associated with a declin...

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Autores principales: Trevor Beaudoin, Tracy A. Stone, Miroslawa Glibowicka, Christina Adams, Yvonne Yau, Saumel Ahmadi, Christine E. Bear, Hartmut Grasemann, Valerie Waters, Charles M. Deber
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/1d3bcf416aa84b6eb2bf558f5d4620b3
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spelling oai:doaj.org-article:1d3bcf416aa84b6eb2bf558f5d4620b32021-12-02T15:08:37ZActivity of a novel antimicrobial peptide against Pseudomonas aeruginosa biofilms10.1038/s41598-018-33016-72045-2322https://doaj.org/article/1d3bcf416aa84b6eb2bf558f5d4620b32018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33016-7https://doaj.org/toc/2045-2322Abstract With the increasing recognition of biofilms in human disease, the development of novel antimicrobial therapies is of critical importance. For example, in patients with cystic fibrosis (CF), the acquisition of host-adapted, chronic Pseudomonas aeruginosa infection is associated with a decline in lung function and increased mortality. Our objective was to test the in vitro efficacy of a membrane-active antimicrobial peptide we designed, termed 6K-F17 (sequence: KKKKKK-AAFAAWAAFAA-NH2), against multidrug resistant P. aeruginosa biofilms. This peptide displays high antimicrobial activity against a range of pathogenic bacteria, yet is non-hemolytic to human erythrocytes and non-toxic to human bronchial epithelial cells. In the present work, P. aeruginosa strain PAO1, and four multidrug resistant (MDR) isolates from chronically infected CF individuals, were grown as 48-hour biofilms in a static biofilm slide chamber model. These biofilms were then exposed to varying concentrations of 6K-F17 alone, or in the presence of tobramycin, prior to confocal imaging. Biofilm biovolume and viability were assessed. 6K-F17 was able to kill biofilms – even in the presence of sputum – and greatly reduce biofilm biovolume in PAO1 and MDR isolates. Strikingly, when used in conjunction with tobramycin, low doses of 6K-F17 significantly potentiated tobramycin killing, leading to biofilm destruction.Trevor BeaudoinTracy A. StoneMiroslawa GlibowickaChristina AdamsYvonne YauSaumel AhmadiChristine E. BearHartmut GrasemannValerie WatersCharles M. DeberNature PortfolioarticleBiovolumeMultidrug Resistance (MDR)Cationic Antimicrobial Peptides (CAPs)Colony Forming Units Per Ml (CFU/mL)Cystic Fibrosis Bronchial Epithelial Cells (CFBE)MedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution DOAJ
collection DOAJ
language EN
topic Biovolume
Multidrug Resistance (MDR)
Cationic Antimicrobial Peptides (CAPs)
Colony Forming Units Per Ml (CFU/mL)
Cystic Fibrosis Bronchial Epithelial Cells (CFBE)
Medicine
R
Science
Q
spellingShingle Biovolume
Multidrug Resistance (MDR)
Cationic Antimicrobial Peptides (CAPs)
Colony Forming Units Per Ml (CFU/mL)
Cystic Fibrosis Bronchial Epithelial Cells (CFBE)
Medicine
R
Science
Q
Trevor Beaudoin
Tracy A. Stone
Miroslawa Glibowicka
Christina Adams
Yvonne Yau
Saumel Ahmadi
Christine E. Bear
Hartmut Grasemann
Valerie Waters
Charles M. Deber
Activity of a novel antimicrobial peptide against Pseudomonas aeruginosa biofilms
description Abstract With the increasing recognition of biofilms in human disease, the development of novel antimicrobial therapies is of critical importance. For example, in patients with cystic fibrosis (CF), the acquisition of host-adapted, chronic Pseudomonas aeruginosa infection is associated with a decline in lung function and increased mortality. Our objective was to test the in vitro efficacy of a membrane-active antimicrobial peptide we designed, termed 6K-F17 (sequence: KKKKKK-AAFAAWAAFAA-NH2), against multidrug resistant P. aeruginosa biofilms. This peptide displays high antimicrobial activity against a range of pathogenic bacteria, yet is non-hemolytic to human erythrocytes and non-toxic to human bronchial epithelial cells. In the present work, P. aeruginosa strain PAO1, and four multidrug resistant (MDR) isolates from chronically infected CF individuals, were grown as 48-hour biofilms in a static biofilm slide chamber model. These biofilms were then exposed to varying concentrations of 6K-F17 alone, or in the presence of tobramycin, prior to confocal imaging. Biofilm biovolume and viability were assessed. 6K-F17 was able to kill biofilms – even in the presence of sputum – and greatly reduce biofilm biovolume in PAO1 and MDR isolates. Strikingly, when used in conjunction with tobramycin, low doses of 6K-F17 significantly potentiated tobramycin killing, leading to biofilm destruction.
format article
author Trevor Beaudoin
Tracy A. Stone
Miroslawa Glibowicka
Christina Adams
Yvonne Yau
Saumel Ahmadi
Christine E. Bear
Hartmut Grasemann
Valerie Waters
Charles M. Deber
author_facet Trevor Beaudoin
Tracy A. Stone
Miroslawa Glibowicka
Christina Adams
Yvonne Yau
Saumel Ahmadi
Christine E. Bear
Hartmut Grasemann
Valerie Waters
Charles M. Deber
author_sort Trevor Beaudoin
title Activity of a novel antimicrobial peptide against Pseudomonas aeruginosa biofilms
title_short Activity of a novel antimicrobial peptide against Pseudomonas aeruginosa biofilms
title_full Activity of a novel antimicrobial peptide against Pseudomonas aeruginosa biofilms
title_fullStr Activity of a novel antimicrobial peptide against Pseudomonas aeruginosa biofilms
title_full_unstemmed Activity of a novel antimicrobial peptide against Pseudomonas aeruginosa biofilms
title_sort activity of a novel antimicrobial peptide against pseudomonas aeruginosa biofilms
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/1d3bcf416aa84b6eb2bf558f5d4620b3
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