Alginate Oligosaccharides Inhibit Fungal Cell Growth and Potentiate the Activity of Antifungals against Candida and Aspergillus spp.

The oligosaccharide OligoG, an alginate derived from seaweed, has been shown to have anti-bacterial and anti-biofilm properties and potentiates the activity of selected antibiotics against multi-drug resistant bacteria. The ability of OligoG to perturb fungal growth and potentiate conventional antifungal agents was evaluated using a range of pathogenic fungal strains. Candida (n = 11) and Aspergillus (n = 3) spp. were tested using germ tube assays, LIVE/DEAD staining, scanning electron microscopy (SEM), atomic force microscopy (AFM) and high-throughput minimum inhibition concentration assays (MICs). In general, the strains tested showed a significant dose-dependent reduction in cell growth at ≥6% OligoG as measured by optical density (OD600; P<0.05). OligoG (>0.5%) also showed a significant inhibitory effect on hyphal growth in germ tube assays, although strain-dependent variations in efficacy were observed (P<0.05). SEM and AFM both showed that OligoG (≥2%) markedly disrupted fungal biofilm formation, both alone, and in combination with fluconazole. Cell surface roughness was also significantly increased by the combination treatment (P<0.001). High-throughput robotic MIC screening demonstrated the potentiating effects of OligoG (2, 6, 10%) with nystatin, amphotericin B, fluconazole, miconazole, voriconazole or terbinafine with the test strains. Potentiating effects were observed for the Aspergillus strains with all six antifungal agents, with an up to 16-fold (nystatin) reduction in MIC. Similarly, all the Candida spp. showed potentiation with nystatin (up to 16-fold) and fluconazole (up to 8-fold). These findings demonstrate the antifungal properties of OligoG and suggest a potential role in the management of fungal infections and possible reduction of antifungal toxicity

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

Preparation of Chitosan-graft-poly(vinyl acetate) Copolymers and Their Adsorption of Copper Ion

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