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

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

Pritchard, Manon F., Powell, Lydia C., Khan, Saira, Griffiths, Peter C. ORCID: 0000-0002-6686-1271, Mansour, Omar T., Schweins, Ralf, Beck, Konrad, Buurma, Niklaas J., Dempsey, Christopher E., Wright, Chris J., Rye, Philip D., Hill, Katja E., Thomas, David W. and Ferguson, Elaine L. (2017) The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption. Scientific Reports, 7:44731. ISSN 2045-2322 (Print), 2045-2322 (Online) (doi: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
Additional Information: © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Uncontrolled Keywords: Antimicrobial resistance; Neutron scattering; Novel polymer therapeutic
Subjects: Q Science > QC Physics
Faculty / Department / Research Group: Faculty of Engineering & Science
Faculty of Engineering & Science > Department of Pharmaceutical, Chemical & Environmental Sciences
Last Modified: 20 Nov 2017 11:33
Selected for GREAT 2016: None
Selected for GREAT 2017: GREAT c
Selected for GREAT 2018: None
URI: http://gala.gre.ac.uk/id/eprint/16601

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