Overcoming Drug Resistance with Alginate Oligosaccharides Able To Potentiate the Action of Selected Antibiotics

The uncontrolled, often inappropriate use of antibiotics has resulted in the increasing prevalence of antibiotic-resistant pathogens, with major cost implications for both US and European healthcare systems. We describe the utilization of a low molecular weight oligosaccharide nanomedicine (OligoG) based on the biopolymer alginate, which is able to perturb multi-drug resistant (MDR) bacteria by modulating biofilm formation/persistence and reducing resistance to antibiotic treatment; evident using conventional and robotic MIC screening and microscopic analyses of biofilm structure. OligoG increased the efficacy of conventional antibiotics (up to 512-fold) against important MDR pathogens including Pseudomonas, Acinetobacter and Burkholderia spp., appearing to be effective with several classes of antibiotic (i.e. macrolides, β-lactams, tetracyclines). Using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) increasing concentrations of alginate oligomer (2, 6 and 10%) were shown 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 study demonstrates the feasibility of reducing the tolerance of wound biofilms to antibiotics with the use of specific alginate preparations.