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The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption

Pritchard, Manon F. ORCID: https://orcid.org/0000-0002-5135-4744, Powell, Lydia C. ORCID: https://orcid.org/0000-0002-8641-0160, Khan, Saira, Griffiths, Peter C., Mansour, Omar T., Schweins, Ralf, Beck, Konrad ORCID: https://orcid.org/0000-0001-5098-9484, Buurma, Niklaas J. ORCID: https://orcid.org/0000-0003-0260-5057, Dempsey, Christopher E., Wright, Chris J., Rye, Philip D., Hill, Katja E. ORCID: https://orcid.org/0000-0002-8590-0117, Thomas, David W. ORCID: https://orcid.org/0000-0001-7319-5820 and Ferguson, Elaine L. ORCID: https://orcid.org/0000-0002-0125-0234 2017. The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption. Scientific Reports 7 , 44731. 10.1038/srep44731

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Abstract

Concerns about acquisition of antibiotic resistance have led to increasing demand for new antimicrobial therapies. OligoG CF-5/20 is an alginate oligosaccharide previously shown to have antimicrobial and antibiotic potentiating activity. We investigated the structural modification of the bacterial cell wall by OligoG CF-5/20 and its effect on membrane permeability. Binding of OligoG CF-5/20 to the bacterial cell surface was demonstrated in Gram-negative bacteria. Permeability assays revealed that OligoG CF-5/20 had virtually no membrane-perturbing effects. Lipopolysaccharide (LPS) surface charge and aggregation were unaltered in the presence of OligoG CF-5/20. Small angle neutron scattering and circular dichroism spectroscopy showed no substantial change to the structure of LPS in the presence of OligoG CF-5/20, however, isothermal titration calorimetry demonstrated a weak calcium-mediated interaction. Metabolomic analysis confirmed no change in cellular metabolic response to a range of osmolytes when treated with OligoG CF-5/20. This data shows that, although weak interactions occur between LPS and OligoG CF-5/20 in the presence of calcium, the antimicrobial effects of OligoG CF-5/20 are not related to the induction of structural alterations in the LPS or cell permeability. These results suggest a novel mechanism of action that may avoid the common route in acquisition of resistance via LPS structural modification.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Chemistry
Subjects: R Medicine > RK Dentistry
Publisher: Nature Publishing Group
ISSN: 2045-2322
Funders: STFC
Date of First Compliant Deposit: 28 March 2017
Date of Acceptance: 13 February 2017
Last Modified: 06 Jan 2024 03:24
URI: https://orca.cardiff.ac.uk/id/eprint/98645

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