title: Alginate oligosaccharides inhibit fungal cell growth and potentiate the activity of antifungals against Candida and Aspergillus spp.
abstract: 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.
authors.affiliation: Department of Bioprocess Technology, SINTEF Materials and Chemistry, N-7465 Trondheim, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Tøndervik
authors.affiliation: Department of Bioprocess Technology, SINTEF Materials and Chemistry, N-7465 Trondheim, Norway.
authors.forename: Håvard
authors.initials: H
authors.lastname: Sletta
authors.affiliation: Department of Bioprocess Technology, SINTEF Materials and Chemistry, N-7465 Trondheim, Norway.
authors.forename: Geir
authors.initials: G
authors.lastname: Klinkenberg
authors.affiliation: Advanced Therapies Group, Tissue Engineering and Reparative Dentistry, Cardiff University School of Dentistry, Cardiff, CF14 4XY, United Kingdom.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Emanuel
authors.affiliation: Advanced Therapies Group, Tissue Engineering and Reparative Dentistry, Cardiff University School of Dentistry, Cardiff, CF14 4XY, United Kingdom.
authors.forename: Lydia C
authors.initials: LC
authors.lastname: Powell
authors.affiliation: Advanced Therapies Group, Tissue Engineering and Reparative Dentistry, Cardiff University School of Dentistry, Cardiff, CF14 4XY, United Kingdom.
authors.forename: Manon F
authors.initials: MF
authors.lastname: Pritchard
authors.affiliation: Advanced Therapies Group, Tissue Engineering and Reparative Dentistry, Cardiff University School of Dentistry, Cardiff, CF14 4XY, United Kingdom.
authors.forename: Saira
authors.initials: S
authors.lastname: Khan
authors.affiliation: Advanced Therapies Group, Tissue Engineering and Reparative Dentistry, Cardiff University School of Dentistry, Cardiff, CF14 4XY, United Kingdom.
authors.forename: Kieron M
authors.initials: KM
authors.lastname: Craine
authors.affiliation: AlgiPharma AS, Industriveien 33, N-1337 Sandvika, Norway.
authors.forename: Edvar
authors.initials: E
authors.lastname: Onsøyen
authors.affiliation: AlgiPharma AS, Industriveien 33, N-1337 Sandvika, Norway.
authors.forename: Phil D
authors.initials: PD
authors.lastname: Rye
authors.affiliation: Centre for NanoHealth, Systems and Process Engineering Centre, College of Engineering, Swansea University, Swansea, SA2 8PP, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Wright
authors.affiliation: Advanced Therapies Group, Tissue Engineering and Reparative Dentistry, Cardiff University School of Dentistry, Cardiff, CF14 4XY, United Kingdom.
authors.forename: David W
authors.initials: DW
authors.lastname: Thomas
authors.affiliation: Advanced Therapies Group, Tissue Engineering and Reparative Dentistry, Cardiff University School of Dentistry, Cardiff, CF14 4XY, United Kingdom.
authors.forename: Katja E
authors.initials: KE
authors.lastname: Hill
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000166:cytology* / Q000187:drug effects*; D002175:Candida / Q000166:cytology* / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D019281:Dimerization; D004357:Drug Synergism; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009844:Oligosaccharides / Q000737:chemistry*
chemical_list: D000464:Alginates; D000935:Antifungal Agents; D006603:Hexuronic Acids; D009844:Oligosaccharides; D020723:Glucuronic Acid