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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.

, Powell, Lydia C.

, Khan, Saira, Griffiths, Peter C., 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. 10.1038/srep44731

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Official URL: http://dx.doi.org/10.1038/srep44731

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