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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
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa64609
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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 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.
Keywords: Alginate oligosaccharide, mannuronic acid, guluronic acid, Pseudomonas aeruginosa, biofilm, calcium
College: Faculty of Medicine, Health and Life Sciences
Funders: 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.
Issue: 9
Start Page: 1366