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ACS Chem Biol DOI:10.1021/cb900243b

Characterization of plant-derived saponin natural products against Candida albicans.

Publication TypeJournal Article
Year of Publication2010
AuthorsColeman, JJ, Okoli, I, Tegos, GP, Holson, EB, Wagner, FF, Hamblin, MR, Mylonakis, E
JournalACS Chem Biol
Volume5
Issue3
Pages321-32
Date Published2010 Mar 19
ISSN1554-8937
KeywordsAnimals, Antifungal Agents, Candida albicans, Candidiasis, Drug Interactions, Erythrocytes, Fluconazole, Hemolysis, Humans, Microbial Sensitivity Tests, Osmotic Pressure, Photochemistry, Plant Extracts, Saponins, Sheep
Abstract

Candida albicans is an opportunistic fungal pathogen capable of life-threatening disseminated infections particularly in immunocompromised patients. Resistance to many clinically used antifungal agents has created a need to identify and develop a new generation of compounds for therapeutic use. A compound screen to identify potential antifungal natural products was undertaken, identifying 12 saponins, some of which have not been previously described. In the Caenorhabditis elegans model, some saponins conferred nematode survival comparable to that of amphotericin B. Of the 12 antifungal saponins identified, two were selected for further analysis. C. albicans isolates were inhibited by these compounds at relatively low concentrations (16 and 32 microg mL(-1)) including isolates resistant to clinically used antifungal agents. C. albicans hyphae and biofilm formation were also disrupted in the presence of these natural products, and studies demonstrate that fungal cells in the presence of saponins are more susceptible to salt-induced osmotic stress. Although saponins are known for their hemolytic activity, no hemolysis of erythrocytes was observed at three times the minimal inhibitory concentration for C. albicans, suggesting the saponins may have a preference for binding to fungal ergosterol when compared to cholesterol. Importantly, when used in combination with photosensitizer compounds, the fungus displayed increased susceptibility to photodynamic inactivation due to the ability of the saponins to increase cell permeability, thereby facilitating penetration of the photosensitizers. The large proportion of compounds identified as antifungal agents containing saponin structural features suggests it may be a suitable chemical scaffold for a new generation of antifungal compounds.

DOI10.1021/cb900243b
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/20099897?dopt=Abstract

Alternate JournalACS Chem. Biol.
PubMed ID20099897
PubMed Central IDPMC2965462
Grant ListR01 AI075286 / AI / NIAID NIH HHS / United States
T32 AI007061 / AI / NIAID NIH HHS / United States
N01CO12400 / CA / NCI NIH HHS / United States
R01 AI050875-06 / AI / NIAID NIH HHS / United States
R01 AI050875 / AI / NIAID NIH HHS / United States
R01 AI050875-08 / AI / NIAID NIH HHS / United States
N01-CO-12400 / CO / NCI NIH HHS / United States
R01 AI075286-03 / AI / NIAID NIH HHS / United States