title: Overcoming drug resistance with alginate oligosaccharides able to potentiate the action of selected antibiotics.
abstract: The uncontrolled, often inappropriate use of antibiotics has resulted in the increasing prevalence of antibiotic-resistant pathogens, with major cost implications for both United States and European health care systems. We describe the utilization of a low-molecular-weight oligosaccharide nanomedicine (OligoG), based on the biopolymer alginate, which is able to perturb multidrug-resistant (MDR) bacteria by modulating biofilm formation and persistence and reducing resistance to antibiotic treatment, as evident using conventional and robotic MIC screening and microscopic analyses of biofilm structure. OligoG increased (up to 512-fold) the efficacy of conventional antibiotics against important MDR pathogens, including Pseudomonas, Acinetobacter, and Burkholderia spp., appearing to be effective with several classes of antibiotic (i.e., macrolides, β-lactams, and tetracyclines). Using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM), increasing concentrations (2%, 6%, and 10%) of alginate oligomer were shown to have a direct effect on the quality of the biofilms produced and on the health of the cells within that biofilm. Biofilm growth was visibly weakened in the presence of 10% OligoG, as seen by decreased biomass and increased intercellular spaces, with the bacterial cells themselves becoming distorted and uneven due to apparently damaged cell membranes. This report demonstrates the feasibility of reducing the tolerance of wound biofilms to antibiotics with the use of specific alginate preparations.
authors: Wound Biology Group, Tissue Engineering and Reparative Dentistry, Cardiff University School of Dentistry, Cardiff, United Kingdom.
authors: Saira
authors: S
authors: Khan
authors: Anne
authors: A
authors: Tøndervik
authors: Håvard
authors: H
authors: Sletta
authors: Geir
authors: G
authors: Klinkenberg
authors: Charlotte
authors: C
authors: Emanuel
authors: Edvar
authors: E
authors: Onsøyen
authors: Rolf
authors: R
authors: Myrvold
authors: Robin A
authors: RA
authors: Howe
authors: Timothy R
authors: TR
authors: Walsh
authors: Katja E
authors: KE
authors: Hill
authors: David W
authors: DW
authors: Thomas
mesh_terms: D000150:Acinetobacter / Q000187:drug effects / Q000235:genetics; D000464:Alginates / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019117:Burkholderia / Q000187:drug effects / Q000235:genetics; D004347:Drug Interactions; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004755:Enterobacteriaceae / Q000187:drug effects / Q000235:genetics; D005838:Genotype; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D009844:Oligosaccharides / Q000737:chemistry / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics; D019533:Streptococcus oralis / Q000187:drug effects / Q000235:genetics
chemical_list: D000464:Alginates; D000900:Anti-Bacterial Agents; D006603:Hexuronic Acids; D009844:Oligosaccharides; D020723:Glucuronic Acid