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Exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent Pseudomonas aeruginosa biofilms
Bacterial biofilms present a significant medical challenge because they are recalcitrant to current therapeutic regimes. A key component of biofilm formation in the opportunistic human pathogen Pseudomonas aeruginosa is the biosynthesis of the exopolysaccharides Pel and Psl, which are involved in th...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928890/ https://www.ncbi.nlm.nih.gov/pubmed/27386527 http://dx.doi.org/10.1126/sciadv.1501632 |
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author | Baker, Perrin Hill, Preston J. Snarr, Brendan D. Alnabelseya, Noor Pestrak, Matthew J. Lee, Mark J. Jennings, Laura K. Tam, John Melnyk, Roman A. Parsek, Matthew R. Sheppard, Donald C. Wozniak, Daniel J. Howell, P. Lynne |
author_facet | Baker, Perrin Hill, Preston J. Snarr, Brendan D. Alnabelseya, Noor Pestrak, Matthew J. Lee, Mark J. Jennings, Laura K. Tam, John Melnyk, Roman A. Parsek, Matthew R. Sheppard, Donald C. Wozniak, Daniel J. Howell, P. Lynne |
author_sort | Baker, Perrin |
collection | PubMed |
description | Bacterial biofilms present a significant medical challenge because they are recalcitrant to current therapeutic regimes. A key component of biofilm formation in the opportunistic human pathogen Pseudomonas aeruginosa is the biosynthesis of the exopolysaccharides Pel and Psl, which are involved in the formation and maintenance of the structural biofilm scaffold and protection against antimicrobials and host defenses. Given that the glycoside hydrolases PelA(h) and PslG(h) encoded in the pel and psl biosynthetic operons, respectively, are utilized for in vivo exopolysaccharide processing, we reasoned that these would provide specificity to target P. aeruginosa biofilms. Evaluating these enzymes as potential therapeutics, we demonstrate that these glycoside hydrolases selectively target and degrade the exopolysaccharide component of the biofilm matrix. PelA(h) and PslG(h) inhibit biofilm formation over a 24-hour period with a half maximal effective concentration (EC(50)) of 69.3 ± 1.2 and 4.1 ± 1.1 nM, respectively, and are capable of disrupting preexisting biofilms in 1 hour with EC(50) of 35.7 ± 1.1 and 12.9 ± 1.1 nM, respectively. This treatment was effective against clinical and environmental P. aeruginosa isolates and reduced biofilm biomass by 58 to 94%. These noncytotoxic enzymes potentiated antibiotics because the addition of either enzyme to a sublethal concentration of colistin reduced viable bacterial counts by 2.5 orders of magnitude when used either prophylactically or on established 24-hour biofilms. In addition, PelA(h) was able to increase neutrophil killing by ~50%. This work illustrates the feasibility and benefits of using bacterial exopolysaccharide biosynthetic glycoside hydrolases to develop novel antibiofilm therapeutics. |
format | Online Article Text |
id | pubmed-4928890 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-49288902016-07-06 Exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent Pseudomonas aeruginosa biofilms Baker, Perrin Hill, Preston J. Snarr, Brendan D. Alnabelseya, Noor Pestrak, Matthew J. Lee, Mark J. Jennings, Laura K. Tam, John Melnyk, Roman A. Parsek, Matthew R. Sheppard, Donald C. Wozniak, Daniel J. Howell, P. Lynne Sci Adv Research Articles Bacterial biofilms present a significant medical challenge because they are recalcitrant to current therapeutic regimes. A key component of biofilm formation in the opportunistic human pathogen Pseudomonas aeruginosa is the biosynthesis of the exopolysaccharides Pel and Psl, which are involved in the formation and maintenance of the structural biofilm scaffold and protection against antimicrobials and host defenses. Given that the glycoside hydrolases PelA(h) and PslG(h) encoded in the pel and psl biosynthetic operons, respectively, are utilized for in vivo exopolysaccharide processing, we reasoned that these would provide specificity to target P. aeruginosa biofilms. Evaluating these enzymes as potential therapeutics, we demonstrate that these glycoside hydrolases selectively target and degrade the exopolysaccharide component of the biofilm matrix. PelA(h) and PslG(h) inhibit biofilm formation over a 24-hour period with a half maximal effective concentration (EC(50)) of 69.3 ± 1.2 and 4.1 ± 1.1 nM, respectively, and are capable of disrupting preexisting biofilms in 1 hour with EC(50) of 35.7 ± 1.1 and 12.9 ± 1.1 nM, respectively. This treatment was effective against clinical and environmental P. aeruginosa isolates and reduced biofilm biomass by 58 to 94%. These noncytotoxic enzymes potentiated antibiotics because the addition of either enzyme to a sublethal concentration of colistin reduced viable bacterial counts by 2.5 orders of magnitude when used either prophylactically or on established 24-hour biofilms. In addition, PelA(h) was able to increase neutrophil killing by ~50%. This work illustrates the feasibility and benefits of using bacterial exopolysaccharide biosynthetic glycoside hydrolases to develop novel antibiofilm therapeutics. American Association for the Advancement of Science 2016-05-20 /pmc/articles/PMC4928890/ /pubmed/27386527 http://dx.doi.org/10.1126/sciadv.1501632 Text en Copyright © 2016, The Authors http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Baker, Perrin Hill, Preston J. Snarr, Brendan D. Alnabelseya, Noor Pestrak, Matthew J. Lee, Mark J. Jennings, Laura K. Tam, John Melnyk, Roman A. Parsek, Matthew R. Sheppard, Donald C. Wozniak, Daniel J. Howell, P. Lynne Exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent Pseudomonas aeruginosa biofilms |
title | Exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent Pseudomonas aeruginosa biofilms |
title_full | Exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent Pseudomonas aeruginosa biofilms |
title_fullStr | Exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent Pseudomonas aeruginosa biofilms |
title_full_unstemmed | Exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent Pseudomonas aeruginosa biofilms |
title_short | Exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent Pseudomonas aeruginosa biofilms |
title_sort | exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent pseudomonas aeruginosa biofilms |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928890/ https://www.ncbi.nlm.nih.gov/pubmed/27386527 http://dx.doi.org/10.1126/sciadv.1501632 |
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