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Issue 3, 2012
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Molecular basis for fungicidal action of neothyonidioside, a triterpene glycoside from the sea cucumber, Australostichopus mollis

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Abstract

Neothyonidioside is a triterpene glycoside (TG) isolated from the sea cucumber, Australostichopus mollis, that is potently cytotoxic to S. cerevisiae, but does not permeabilize cellular membranes. We mutagenized S. cerevisiae and isolated a neothionidioside-resistant (neoR) strain. Using synthetic genetic array mapping and sequencing, we identified NCP1 as the resistance locus. Quantitative HPLC revealed that neoR/ncp1 mutants have reduced ergosterol content. Ergosterol added to growth media reversed toxicity, demonstrating that neothionidioside binds directly to ergosterol, similar to the polyene natamycin. Ergosterol synthesis inhibitors ketoconazole and atorvastatin conferred resistance to neothionidioside in a dose-dependent manner showing that a threshold ergosterol concentration is required for toxicity. A genome-wide screen of deletion mutants against neothionidioside revealed hypersensitivity of many of the component genes in the ESCRT complexes relating to multivesicular body formation. Confocal microscopy of cells stained with a vital dye showed blockage at this step. Thus, we propose neothionidioside may affect membrane curvature and fusion capability in the endosome-vacuole pathway.

Graphical abstract: Molecular basis for fungicidal action of neothyonidioside, a triterpene glycoside from the sea cucumber, Australostichopus mollis

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Publication details

The article was received on 14 Oct 2011, accepted on 14 Dec 2011 and first published on 25 Jan 2012


Article type: Paper
DOI: 10.1039/C2MB05426D
Citation: Mol. BioSyst., 2012,8, 902-912
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    Molecular basis for fungicidal action of neothyonidioside, a triterpene glycoside from the sea cucumber, Australostichopus mollis

    P. Yibmantasiri, D. C. Leahy, B. P. Busby, S. A. Angermayr, A. G. Sorgo, K. Boeger, R. Heathcott, J. M. Barber, G. Moraes, J. H. Matthews, P. T. Northcote, P. H. Atkinson and D. S. Bellows, Mol. BioSyst., 2012, 8, 902
    DOI: 10.1039/C2MB05426D

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