A Novel Antifungal Alginate Oligomer Induces Impaired Fungal Hyphae Formation

Method: The effect of alginate oligomers (2, 6 and 10%) on the growth of two important fungal pathogens Candida and Aspergillus spp. was tested using a batch growth assay (in broth), and a germ tube assay (to detect hyphal formation in horse serum), while biofilm formation was determined using cell imaging (LIVE/DEAD staining; scanning electron microscopy, SEM; and atomic force microscopy, AFM).

Result: Alginate oligomers effectively inhibited the growth of all the fungal strains tested in a concentration-dependent manner and had a pronounced effect on hyphae growth in the germ tube assay, with far fewer OligoG-treated cells producing hyphae than the control.  Alginate oligomer treatment also resulted in biofilm disruption, as demonstrated by increased cell death (LIVE/DEAD staining) and marked decreases in biofilm density (SEM).  Furthermore, AFM revealed that treatment produced distinctive morphological changes (cell flattening) in Candida cells, which were enhanced when used in conjunction with the antifungal fluconazole.

Conclusion: These in vitro studies demonstrate the ability of alginate oligomers to modify the behaviour of fungal pathogens, particularly in terms of biofilm formation.  Biofilm modification and the inhibition of hyphae formation are important mechanisms wherein alginate oligomers may affect the observed in vitro potentiation of antifungal agents.