The effect of alginate oligosaccharides on the mechanical properties of Gram-negative biofilms

Powell LC, Sowedan A, Khan S, Wright CJ, Hawkins K, Onsøyen E, Myrvold R, Hill KE, Thomas DW.
Biofouling. 2013 Apr;29(4):413-21. doi: 10.1080/08927014.2013.777954.

External link to Pubmed.gov

Abstract

The influence of a novel, safe antibiofilm therapy on the mechanical properties of Pseudomonas aeruginosa and Acinetobacter baumannii biofilms in vitro was characterized. A multiscale approach employing atomic force microscopy (AFM) and rheometry was used to quantify the mechanical disruption of the biofilms by a therapeutic polymer based on a low-molecular weight alginate oligosaccharide (OligoG). AFM demonstrated structural alterations in the biofilms exposed to OligoG, with significantly lower Young’s moduli than the untreated biofilms, (149 MPa vs 242 MPa; p < 0.05), a decreased resistance to hydrodynamic shear and an increased surface irregularity (Ra) in the untreated controls (35.2 nm ± 7.6 vs 12.1 nm ± 5.4; p < 0.05). Rheology demonstrated that increasing clinically relevant concentrations of OligoG (<10%) were associated with an increasing phase angle (δ) over a wide range of frequencies (0.1-10 Hz). These results highlight the utility of these techniques for the study of three-dimensional biofilms and for quantifying novel disruption therapies in vitro.

For further information, please contact:
Philip D. Rye R&D Director; phil.rye@algipharma.com

April 2013

Overcoming drug resistance with alginate oligosaccharides able to potentiate the action of selected antibiotics

Khan S, Tøndervik A, Sletta H, Klinkenberg G, Emanuel C, Onsøyen E, Myrvold R, Howe RA, Walsh TR, Hill KE, Thomas DW.
Antimicrob Agents Chemother. 2012 Oct;56(10):5134-41. doi: 10.1128/AAC.00525-12. Epub 2012 Jul 23.

External link to Pubmed.gov

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.

For further information, please contact:
Philip D. Rye R&D Director; phil.rye@algipharma.com

August 2012