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Gymnemic acids inhibit hyphal growth and virulence in Candida albicans.

Abstract

Candida albicans is an opportunistic and polymorphic fungal pathogen that causes mucosal, disseminated and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm formation. Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. Here, we have identified the triterpenoid saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic traditional medicinal plant used to treat diabetes. Purified GAs had no effect on the growth and viability of C. albicans yeast cells but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. Hence, GAs could be useful for various antifungal applications due to their traditional use in herbal medicine.

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  • Authors+Show Affiliations

    ,

    Division of Biology, Kansas State University, Manhattan, Kansas, United States of America ; Institut Pasteur, Unité Biologie et Pathogénicité Fongiques, Département Génomes et Génétique, Paris, France ; INRA, USC2019, Paris, France.

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    Source

    PloS one 8:9 2013 pg e74189

    MeSH

    Animals
    Antifungal Agents
    Caenorhabditis elegans
    Candida albicans
    Gymnema sylvestre
    Humans
    Hyphae
    Plant Extracts
    Saponins
    Spores, Fungal
    Triterpenes
    Virulence

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24040201

    Citation

    * When formatting your citation, note that all book, journal, and database titles should be italicized* Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Gymnemic acids inhibit hyphal growth and virulence in Candida albicans. AU - Vediyappan,Govindsamy, AU - Dumontet,Vincent, AU - Pelissier,Franck, AU - d'Enfert,Christophe, Y1 - 2013/09/11/ PY - 2013/04/22/received PY - 2013/07/30/accepted PY - 2013/9/17/entrez PY - 2013/9/17/pubmed PY - 2014/6/4/medline SP - e74189 EP - e74189 JF - PloS one JO - PLoS ONE VL - 8 IS - 9 N2 - Candida albicans is an opportunistic and polymorphic fungal pathogen that causes mucosal, disseminated and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm formation. Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. Here, we have identified the triterpenoid saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic traditional medicinal plant used to treat diabetes. Purified GAs had no effect on the growth and viability of C. albicans yeast cells but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. Hence, GAs could be useful for various antifungal applications due to their traditional use in herbal medicine. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24040201/Gymnemic_acids_inhibit_hyphal_growth_and_virulence_in_Candida_albicans_ L2 - http://dx.plos.org/10.1371/journal.pone.0074189 DB - PRIME DP - Unbound Medicine ER -