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

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dc.cclicenceCC-BYen
dc.contributor.authorPritchard, Manon F.
dc.contributor.authorPowell, Lydia C.
dc.contributor.authorKhan, Saira
dc.contributor.authorGriffiths, Peter C.
dc.contributor.authorMansour, Omar T.
dc.contributor.authorSchweins, Ralf
dc.contributor.authorBeck, Konrad
dc.contributor.authorBuurma, Niklaas J.
dc.contributor.authorDempsey, Christopher E
dc.contributor.authorWright, Chris J
dc.contributor.authorRye, Philip D
dc.contributor.authorHill, Katja E.
dc.contributor.authorThomas, David W.
dc.contributor.authorFerguson, Elaine L.
dc.date.accessioned2019-09-05T10:38:26Z
dc.date.available2019-09-05T10:38:26Z
dc.date.issued2017-03-31
dc.descriptionopen access articleen
dc.description.abstractConcerns 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.en
dc.exception.ref2021codes254aen
dc.funderNo external funderen
dc.identifier.citationPritchard, M.F. et al. (2017) The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption. Scientific Reports, 7, 44731en
dc.identifier.doihttps://doi.org/10.1038/srep44731
dc.identifier.urihttps://gala.gre.ac.uk/id/eprint/16601/
dc.identifier.urihttps://www.dora.dmu.ac.uk/handle/2086/18404
dc.language.isoenen
dc.peerreviewedYesen
dc.publisherSpringer Natureen
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en
dc.titleThe antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruptionen
dc.typeArticleen

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