Cargando…
Polymers for binding of the gram-positive oral pathogen Streptococcus mutans
Streptococcus mutans is the most significant pathogenic bacterium implicated in the formation of dental caries and, both directly and indirectly, has been associated with severe conditions such as multiple sclerosis, cerebrovascular and peripheral artery disease. Polymers able to selectively bind S....
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495209/ https://www.ncbi.nlm.nih.gov/pubmed/28672031 http://dx.doi.org/10.1371/journal.pone.0180087 |
_version_ | 1783247771053064192 |
---|---|
author | Magennis, Eugene P. Francini, Nora Mastrotto, Francesca Catania, Rosa Redhead, Martin Fernandez-Trillo, Francisco Bradshaw, David Churchley, David Winzer, Klaus Alexander, Cameron Mantovani, Giuseppe |
author_facet | Magennis, Eugene P. Francini, Nora Mastrotto, Francesca Catania, Rosa Redhead, Martin Fernandez-Trillo, Francisco Bradshaw, David Churchley, David Winzer, Klaus Alexander, Cameron Mantovani, Giuseppe |
author_sort | Magennis, Eugene P. |
collection | PubMed |
description | Streptococcus mutans is the most significant pathogenic bacterium implicated in the formation of dental caries and, both directly and indirectly, has been associated with severe conditions such as multiple sclerosis, cerebrovascular and peripheral artery disease. Polymers able to selectively bind S. mutans and/or inhibit its adhesion to oral tissue in a non-lethal manner would offer possibilities for addressing pathogenicity without selecting for populations resistant against bactericidal agents. In the present work two libraries of 2-(dimethylamino)ethyl methacrylate (pDMAEMA)-based polymers were synthesized with various proportions of either N,N,N-trimethylethanaminium cationic- or sulfobetaine zwitterionic groups. These copolymers where initially tested as potential macromolecular ligands for S. mutans NCTC 10449, whilst Escherichia coli MG1655 was used as Gram-negative control bacteria. pDMAEMA-derived materials with high proportions of zwitterionic repeating units were found to be selective for S. mutans, in both isolated and S. mutans–E. coli mixed bacterial cultures. Fully sulfobetainized pDMAEMA was subsequently found to bind/cluster preferentially Gram-positive S. mutans and S. aureus compared to Gram negative E. coli and V. harveyi. A key initial stage of S. mutans pathogenesis involves a lectin-mediated adhesion to the tooth surface, thus the range of potential macromolecular ligands was further expanded by investigating two glycopolymers bearing α-mannopyranoside and β-galactopyranoside pendant units. Results with these polymers indicated that preferential binding to either S. mutans or E. coli can be obtained by modulating the glycosylation pattern of the chosen multivalent ligands without incurring unacceptable cytotoxicity in a model gastrointestinal cell line. Overall, our results allowed to identify a structure–property relationship for the potential antimicrobial polymers investigated, and suggest that preferential binding to Gram-positive S. mutans could be achieved by fine-tuning of the recognition elements in the polymer ligands. |
format | Online Article Text |
id | pubmed-5495209 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-54952092017-07-18 Polymers for binding of the gram-positive oral pathogen Streptococcus mutans Magennis, Eugene P. Francini, Nora Mastrotto, Francesca Catania, Rosa Redhead, Martin Fernandez-Trillo, Francisco Bradshaw, David Churchley, David Winzer, Klaus Alexander, Cameron Mantovani, Giuseppe PLoS One Research Article Streptococcus mutans is the most significant pathogenic bacterium implicated in the formation of dental caries and, both directly and indirectly, has been associated with severe conditions such as multiple sclerosis, cerebrovascular and peripheral artery disease. Polymers able to selectively bind S. mutans and/or inhibit its adhesion to oral tissue in a non-lethal manner would offer possibilities for addressing pathogenicity without selecting for populations resistant against bactericidal agents. In the present work two libraries of 2-(dimethylamino)ethyl methacrylate (pDMAEMA)-based polymers were synthesized with various proportions of either N,N,N-trimethylethanaminium cationic- or sulfobetaine zwitterionic groups. These copolymers where initially tested as potential macromolecular ligands for S. mutans NCTC 10449, whilst Escherichia coli MG1655 was used as Gram-negative control bacteria. pDMAEMA-derived materials with high proportions of zwitterionic repeating units were found to be selective for S. mutans, in both isolated and S. mutans–E. coli mixed bacterial cultures. Fully sulfobetainized pDMAEMA was subsequently found to bind/cluster preferentially Gram-positive S. mutans and S. aureus compared to Gram negative E. coli and V. harveyi. A key initial stage of S. mutans pathogenesis involves a lectin-mediated adhesion to the tooth surface, thus the range of potential macromolecular ligands was further expanded by investigating two glycopolymers bearing α-mannopyranoside and β-galactopyranoside pendant units. Results with these polymers indicated that preferential binding to either S. mutans or E. coli can be obtained by modulating the glycosylation pattern of the chosen multivalent ligands without incurring unacceptable cytotoxicity in a model gastrointestinal cell line. Overall, our results allowed to identify a structure–property relationship for the potential antimicrobial polymers investigated, and suggest that preferential binding to Gram-positive S. mutans could be achieved by fine-tuning of the recognition elements in the polymer ligands. Public Library of Science 2017-07-03 /pmc/articles/PMC5495209/ /pubmed/28672031 http://dx.doi.org/10.1371/journal.pone.0180087 Text en © 2017 Magennis et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Magennis, Eugene P. Francini, Nora Mastrotto, Francesca Catania, Rosa Redhead, Martin Fernandez-Trillo, Francisco Bradshaw, David Churchley, David Winzer, Klaus Alexander, Cameron Mantovani, Giuseppe Polymers for binding of the gram-positive oral pathogen Streptococcus mutans |
title | Polymers for binding of the gram-positive oral pathogen Streptococcus mutans |
title_full | Polymers for binding of the gram-positive oral pathogen Streptococcus mutans |
title_fullStr | Polymers for binding of the gram-positive oral pathogen Streptococcus mutans |
title_full_unstemmed | Polymers for binding of the gram-positive oral pathogen Streptococcus mutans |
title_short | Polymers for binding of the gram-positive oral pathogen Streptococcus mutans |
title_sort | polymers for binding of the gram-positive oral pathogen streptococcus mutans |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495209/ https://www.ncbi.nlm.nih.gov/pubmed/28672031 http://dx.doi.org/10.1371/journal.pone.0180087 |
work_keys_str_mv | AT magenniseugenep polymersforbindingofthegrampositiveoralpathogenstreptococcusmutans AT francininora polymersforbindingofthegrampositiveoralpathogenstreptococcusmutans AT mastrottofrancesca polymersforbindingofthegrampositiveoralpathogenstreptococcusmutans AT cataniarosa polymersforbindingofthegrampositiveoralpathogenstreptococcusmutans AT redheadmartin polymersforbindingofthegrampositiveoralpathogenstreptococcusmutans AT fernandeztrillofrancisco polymersforbindingofthegrampositiveoralpathogenstreptococcusmutans AT bradshawdavid polymersforbindingofthegrampositiveoralpathogenstreptococcusmutans AT churchleydavid polymersforbindingofthegrampositiveoralpathogenstreptococcusmutans AT winzerklaus polymersforbindingofthegrampositiveoralpathogenstreptococcusmutans AT alexandercameron polymersforbindingofthegrampositiveoralpathogenstreptococcusmutans AT mantovanigiuseppe polymersforbindingofthegrampositiveoralpathogenstreptococcusmutans |