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Alginate oligosaccharides inhibit fungal cell growth and potentiate the activity of antifungals against Candida and Aspergillus spp.

Tøndervik A, Sletta H, Klinkenberg G, Emanuel C, Powell LC, Pritchard MF, Khan S, Craine KM, Onsøyen E, Rye PD, Wright C, Thomas DW, Hill KE - PLoS ONE (2014)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioprocess Technology, SINTEF Materials and Chemistry, N-7465 Trondheim, Norway.

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.

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Germ tube assays.(A) Light microscopy images of Candida albicans (CCUG 39343) cells grown with/without the presence of OligoG, (Scale bar is 100 µm). (B) Percentage of Candida cells producing hyphae for four different strains grown for 2 hours in the presence of OligoG (0, 0.2, 0.5, 2, 6 and 10%). Candida glabrata as a non-hyphae producer was the negative control. *indicates significantly different from the control, (P<0.05).
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pone-0112518-g002: Germ tube assays.(A) Light microscopy images of Candida albicans (CCUG 39343) cells grown with/without the presence of OligoG, (Scale bar is 100 µm). (B) Percentage of Candida cells producing hyphae for four different strains grown for 2 hours in the presence of OligoG (0, 0.2, 0.5, 2, 6 and 10%). Candida glabrata as a non-hyphae producer was the negative control. *indicates significantly different from the control, (P<0.05).

Mentions: Light microscopy images of the germ tube assay revealed that OligoG had a pronounced effect on the hyphal growth of C. albicans CCUG 39343 (Figure 2A) demonstrating a reduced number of cells producing hyphae following treatment with OligoG. The actual concentration of OligoG required to produce an effect however, was species-dependent. The percentage number of cells with hyphal growth decreased significantly using ≥0.5% OligoG for C. albicans 39343 and C. tropicalis 519468, and ≥6% OligoG for C. albicans 90028 when compared to the control (Figure 2B; P<0.05). The pH of the Candida cultures in serum remained between pH 7.2 and 7.5 throughout, showing that the observed effects were not pH related.


Alginate oligosaccharides inhibit fungal cell growth and potentiate the activity of antifungals against Candida and Aspergillus spp.

Tøndervik A, Sletta H, Klinkenberg G, Emanuel C, Powell LC, Pritchard MF, Khan S, Craine KM, Onsøyen E, Rye PD, Wright C, Thomas DW, Hill KE - PLoS ONE (2014)

Germ tube assays.(A) Light microscopy images of Candida albicans (CCUG 39343) cells grown with/without the presence of OligoG, (Scale bar is 100 µm). (B) Percentage of Candida cells producing hyphae for four different strains grown for 2 hours in the presence of OligoG (0, 0.2, 0.5, 2, 6 and 10%). Candida glabrata as a non-hyphae producer was the negative control. *indicates significantly different from the control, (P<0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4237368&req=5

pone-0112518-g002: Germ tube assays.(A) Light microscopy images of Candida albicans (CCUG 39343) cells grown with/without the presence of OligoG, (Scale bar is 100 µm). (B) Percentage of Candida cells producing hyphae for four different strains grown for 2 hours in the presence of OligoG (0, 0.2, 0.5, 2, 6 and 10%). Candida glabrata as a non-hyphae producer was the negative control. *indicates significantly different from the control, (P<0.05).
Mentions: Light microscopy images of the germ tube assay revealed that OligoG had a pronounced effect on the hyphal growth of C. albicans CCUG 39343 (Figure 2A) demonstrating a reduced number of cells producing hyphae following treatment with OligoG. The actual concentration of OligoG required to produce an effect however, was species-dependent. The percentage number of cells with hyphal growth decreased significantly using ≥0.5% OligoG for C. albicans 39343 and C. tropicalis 519468, and ≥6% OligoG for C. albicans 90028 when compared to the control (Figure 2B; P<0.05). The pH of the Candida cultures in serum remained between pH 7.2 and 7.5 throughout, showing that the observed effects were not pH related.

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioprocess Technology, SINTEF Materials and Chemistry, N-7465 Trondheim, Norway.

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.

Show MeSH
Related in: MedlinePlus