title: The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption.
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.
authors.affiliation: Advanced Therapies Group, Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, UK.
authors.forename: Manon F
authors.initials: MF
authors.lastname: Pritchard
authors.affiliation: Advanced Therapies Group, Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, UK.
authors.forename: Lydia C
authors.initials: LC
authors.lastname: Powell
authors.affiliation: Advanced Therapies Group, Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, UK.
authors.forename: Saira
authors.initials: S
authors.lastname: Khan
authors.affiliation: Department of Pharmaceutical, Chemical and Environmental Sciences, Faculty of Engineering and Science, University of Greenwich, Medway Campus, Central Avenue, Chatham Maritime, UK.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Griffiths
authors.affiliation: Department of Pharmaceutical, Chemical and Environmental Sciences, Faculty of Engineering and Science, University of Greenwich, Medway Campus, Central Avenue, Chatham Maritime, UK.
authors.forename: Omar T
authors.initials: OT
authors.lastname: Mansour
authors.affiliation: Institut Laue-Langevin, DS/LSS group, 6 rue Jules Horowitz, 38042 Grenoble Cedex 9, France.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schweins
authors.affiliation: Advanced Therapies Group, Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, UK.
authors.forename: Konrad
authors.initials: K
authors.lastname: Beck
authors.affiliation: Physical Organic Chemistry Centre, School of Chemistry, Cardiff University, Cardiff, UK.
authors.forename: Niklaas J
authors.initials: NJ
authors.lastname: Buurma
authors.affiliation: School of Biochemistry, Biomedical Sciences Building, University Walk, Clifton, BS8 1TD, UK.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Dempsey
authors.affiliation: Centre for NanoHealth, Systems and Process Engineering Centre, College of Engineering, Swansea University, Swansea, UK.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Wright
authors.affiliation: AlgiPharma AS, Sandvika, Norway.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Rye
authors.affiliation: Advanced Therapies Group, Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, UK.
authors.forename: Katja E
authors.initials: KE
authors.lastname: Hill
authors.affiliation: Advanced Therapies Group, Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, UK.
authors.forename: David W
authors.initials: DW
authors.lastname: Thomas
authors.affiliation: Advanced Therapies Group, Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, UK.
authors.forename: Elaine L
authors.initials: EL
authors.lastname: Ferguson
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002413:Cations, Divalent / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000166:cytology* / Q000187:drug effects; D013295:Streptococcus mutans / Q000166:cytology* / Q000187:drug effects
chemical_list: D000464:Alginates; D000890:Anti-Infective Agents; D002413:Cations, Divalent; D006603:Hexuronic Acids; D008070:Lipopolysaccharides; D020723:Glucuronic Acid