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

Autor: Pritchard MF; Advanced Therapies Group, School of Dentistry, Cardiff University, Cardiff CF14 4XY, UK., Powell LC; Advanced Therapies Group, School of Dentistry, Cardiff University, Cardiff CF14 4XY, UK.; Microbiology and Infectious Disease Group, Swansea University Medical School, Swansea SA2 8PP, UK., Adams JYM; Advanced Therapies Group, School of Dentistry, Cardiff University, Cardiff CF14 4XY, UK., Menzies G; School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK., Khan S; Advanced Therapies Group, School of Dentistry, Cardiff University, Cardiff CF14 4XY, UK., Tøndervik A; Department of Bioprocess Technology, SINTEF Materials and Chemistry, N-7465 Trondheim, Norway., Sletta H; Department of Bioprocess Technology, SINTEF Materials and Chemistry, N-7465 Trondheim, Norway., Aarstad O; Department of Biotechnology, Norwegian University of Science and Technology, N-7491 Trondheim, Norway., Skjåk-Bræk G; Department of Biotechnology, Norwegian University of Science and Technology, N-7491 Trondheim, Norway., McKenna S; Advanced Therapies Group, School of Dentistry, Cardiff University, Cardiff CF14 4XY, UK., Buurma NJ; Physical Organic Chemistry Centre, School of Chemistry, Cardiff University, Cardiff CF10 3AT, UK., Farnell DJJ; Advanced Therapies Group, School of Dentistry, Cardiff University, Cardiff CF14 4XY, UK., Rye PD; AlgiPharma AS, Industriveien 33, N-1337 Sandvika, Norway., Hill KE; Advanced Therapies Group, School of Dentistry, Cardiff University, Cardiff CF14 4XY, UK., Thomas DW; Advanced Therapies Group, School of Dentistry, Cardiff University, Cardiff CF14 4XY, UK.
Jazyk: angličtina
Zdroj: Biomolecules [Biomolecules] 2023 Sep 08; Vol. 13 (9). Date of Electronic Publication: 2023 Sep 08.
DOI: 10.3390/biom13091366
Abstrakt: 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 (Ca 2+ )-DNA binding within bacterial biofilms and dysregulation of quorum sensing (QS) were key factors in these observed effects. To further investigate the contribution of Ca 2+ binding, G-block (OligoG) and M-block alginate oligosaccharides (OligoM) with comparable average size DPn 19 but contrasting Ca 2+ 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 Ca 2+ -dependent processes but also by electrostatic interactions that are common to both G-block and M-block structures.
Databáze: MEDLINE
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