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Structure–Activity Relationships of Low Molecular Weight Alginate Oligosaccharide Therapy against Pseudomonas aeruginosa

Manon F. Pritchard, Lydia Powell Orcid Logo, Jennifer Y. M. Adams, Georgina Menzies Orcid Logo, Saira Khan, Anne Tøndervik, Håvard Sletta, Olav Aarstad, Gudmund Skjåk-Bræk, Stephen McKenna, Niklaas J. Buurma Orcid Logo, Damian J. J. Farnell Orcid Logo, Philip D. Rye Orcid Logo, Katja E. Hill Orcid Logo, David W. Thomas Orcid Logo

Biomolecules, Volume: 13, Issue: 9, Start page: 1366

Swansea University Author: Lydia Powell Orcid Logo

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DOI (Published version): 10.3390/biom13091366

Abstract

Low molecular weight alginate oligosaccharides have been shown to exhibit anti-microbial activity against a range of multi-drug resistant bacteria, including Pseudomonas aeruginosa. Previous studies suggested that the disruption of calcium (Ca2+)–DNA binding within bacterial biofilms and dysregulati...

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Published in: Biomolecules
ISSN: 2218-273X
Published: MDPI AG 2023
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URI: https://cronfa.swan.ac.uk/Record/cronfa64609
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spelling v2 64609 2023-09-25 Structure–Activity Relationships of Low Molecular Weight Alginate Oligosaccharide Therapy against Pseudomonas aeruginosa 0e7e702952672bcbfdfd4974199202fb 0000-0002-8641-0160 Lydia Powell Lydia Powell true false 2023-09-25 BMS Low molecular weight alginate oligosaccharides have been shown to exhibit anti-microbial activity against a range of multi-drug resistant bacteria, including Pseudomonas aeruginosa. Previous studies suggested that the disruption of calcium (Ca2+)–DNA binding within bacterial biofilms and dysregulation of quorum sensing (QS) were key factors in these observed effects. To further investigate the contribution of Ca2+ binding, G-block (OligoG) and M-block alginate oligosaccharides (OligoM) with comparable average size DPn 19 but contrasting Ca2+ binding properties were prepared. Fourier-transform infrared spectroscopy demonstrated prolonged binding of alginate oligosaccharides to the pseudomonal cell membrane even after hydrodynamic shear treatment. Molecular dynamics simulations and isothermal titration calorimetry revealed that OligoG exhibited stronger interactions with bacterial LPS than OligoM, although this difference was not mirrored by differential reductions in bacterial growth. While confocal laser scanning microscopy showed that both agents demonstrated similar dose-dependent reductions in biofilm formation, OligoG exhibited a stronger QS inhibitory effect and increased potentiation of the antibiotic azithromycin in minimum inhibitory concentration and biofilm assays. This study demonstrates that the anti-microbial effects of alginate oligosaccharides are not purely influenced by Ca2+-dependent processes but also by electrostatic interactions that are common to both G-block and M-block structures. Journal Article Biomolecules 13 9 1366 MDPI AG 2218-273X Alginate oligosaccharide, mannuronic acid, guluronic acid, Pseudomonas aeruginosa, biofilm, calcium 8 9 2023 2023-09-08 10.3390/biom13091366 http://dx.doi.org/10.3390/biom13091366 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University Another institution paid the OA fee This research was funded by the European Union via the Eurostars (TM) Program (EU grant no. 6628); Sêr Cymru II Program, part-funded by Cardiff University and the European Regional Development Fund through the Welsh Government (grant no. 80762-CU176); MucosALG, Research Council of Norway, (NRC grant no. 281920); Cystic Fibrosis Foundation (CFF grant no. ALGIPHAMAIIWO) and with direct funding from AlgiPharma AS to D.W.T and K.E.H. 2023-10-19T15:36:15.7815309 2023-09-25T08:30:10.4961031 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Manon F. Pritchard 1 Lydia Powell 0000-0002-8641-0160 2 Jennifer Y. M. Adams 3 Georgina Menzies 0000-0002-6600-6507 4 Saira Khan 5 Anne Tøndervik 6 Håvard Sletta 7 Olav Aarstad 8 Gudmund Skjåk-Bræk 9 Stephen McKenna 10 Niklaas J. Buurma 0000-0003-0260-5057 11 Damian J. J. Farnell 0000-0003-0662-1927 12 Philip D. Rye 0000-0001-7762-3300 13 Katja E. Hill 0000-0002-8590-0117 14 David W. Thomas 0000-0001-7319-5820 15 64609__28835__4c25683385304e3c89b9ffbaa54d21ab.pdf 64609.VOR.pdf 2023-10-19T15:35:06.5606930 Output 2976405 application/pdf Version of Record true © 2023 by the authors. Licensee MDPI, Basel, Switzerland. Distributed under the terms of a Creative Commons Attribution 4.0 License (CC BY 4.0). true eng https://creativecommons.org/licenses/by/4.0/
title Structure–Activity Relationships of Low Molecular Weight Alginate Oligosaccharide Therapy against Pseudomonas aeruginosa
spellingShingle Structure–Activity Relationships of Low Molecular Weight Alginate Oligosaccharide Therapy against Pseudomonas aeruginosa
Lydia Powell
title_short Structure–Activity Relationships of Low Molecular Weight Alginate Oligosaccharide Therapy against Pseudomonas aeruginosa
title_full Structure–Activity Relationships of Low Molecular Weight Alginate Oligosaccharide Therapy against Pseudomonas aeruginosa
title_fullStr Structure–Activity Relationships of Low Molecular Weight Alginate Oligosaccharide Therapy against Pseudomonas aeruginosa
title_full_unstemmed Structure–Activity Relationships of Low Molecular Weight Alginate Oligosaccharide Therapy against Pseudomonas aeruginosa
title_sort Structure–Activity Relationships of Low Molecular Weight Alginate Oligosaccharide Therapy against Pseudomonas aeruginosa
author_id_str_mv 0e7e702952672bcbfdfd4974199202fb
author_id_fullname_str_mv 0e7e702952672bcbfdfd4974199202fb_***_Lydia Powell
author Lydia Powell
author2 Manon F. Pritchard
Lydia Powell
Jennifer Y. M. Adams
Georgina Menzies
Saira Khan
Anne Tøndervik
Håvard Sletta
Olav Aarstad
Gudmund Skjåk-Bræk
Stephen McKenna
Niklaas J. Buurma
Damian J. J. Farnell
Philip D. Rye
Katja E. Hill
David W. Thomas
format Journal article
container_title Biomolecules
container_volume 13
container_issue 9
container_start_page 1366
publishDate 2023
institution Swansea University
issn 2218-273X
doi_str_mv 10.3390/biom13091366
publisher MDPI AG
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
url http://dx.doi.org/10.3390/biom13091366
document_store_str 1
active_str 0
description Low molecular weight alginate oligosaccharides have been shown to exhibit anti-microbial activity against a range of multi-drug resistant bacteria, including Pseudomonas aeruginosa. Previous studies suggested that the disruption of calcium (Ca2+)–DNA binding within bacterial biofilms and dysregulation of quorum sensing (QS) were key factors in these observed effects. To further investigate the contribution of Ca2+ binding, G-block (OligoG) and M-block alginate oligosaccharides (OligoM) with comparable average size DPn 19 but contrasting Ca2+ binding properties were prepared. Fourier-transform infrared spectroscopy demonstrated prolonged binding of alginate oligosaccharides to the pseudomonal cell membrane even after hydrodynamic shear treatment. Molecular dynamics simulations and isothermal titration calorimetry revealed that OligoG exhibited stronger interactions with bacterial LPS than OligoM, although this difference was not mirrored by differential reductions in bacterial growth. While confocal laser scanning microscopy showed that both agents demonstrated similar dose-dependent reductions in biofilm formation, OligoG exhibited a stronger QS inhibitory effect and increased potentiation of the antibiotic azithromycin in minimum inhibitory concentration and biofilm assays. This study demonstrates that the anti-microbial effects of alginate oligosaccharides are not purely influenced by Ca2+-dependent processes but also by electrostatic interactions that are common to both G-block and M-block structures.
published_date 2023-09-08T15:36:16Z
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