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    Proteomic analysis of proteins released from growth-arrested Candida albicans following exposure to caspofungin


    Kelly, Judy and Kavanagh, Kevin (2010) Proteomic analysis of proteins released from growth-arrested Candida albicans following exposure to caspofungin. Medical Mycology, 48 (4). pp. 598-605. ISSN 1460-2709

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    Abstract

    The echinocandins (e.g., caspofungin) are a relatively new class of antifungal drugs that function by inhibiting the synthesis of β-1,3-glucan in the cell wall and thus lead to lysis of the cell. In this work the effect of caspofungin on the release of peptides from non-growing cells of the yeast Candida albicans that had been exposed to the drug was monitored. Exposure to 0.19 μg/ml caspofungin resulted in the release of amino acids from cells and of both small and large molecular weight proteins as demonstrated by 1- and 2-dimensional gel electrophoresis. Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-ToF) mass spectrometry was employed to identify a number of escaped peptides that were found to have increased in intensity upon exposure to the drug. A number of wall-associated proteins (e.g., phosphoglycerate kinase) and a number of glycolytic enzymes (phosphoglycerate mutase 1, fructose-bisphosphate aldolase) were identified. Importantly, several released proteins (e.g., pyruvate kinase, enolase 1, phosphoglycerate mutase, glyceraldehydes 3-phosphate dehydrogenase, fructose bisphosphate aldolase and alcohol dehydrogenase 1) are highly immunogenic in nature. The results presented here demonstrate that non-growing C. albicans cells are susceptible to the effect of caspofungin and that the caspofungin-mediated release of proteins from such cells could lead to a stronger immune response in vivo. This report illustrates that, in addition to hampering cell wall synthesis, caspofungin may also interfere with the permeability of the fungal cell wall.

    Item Type: Article
    Keywords: antifungal; Candida; caspofungin; proteomics; proteins;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 11109
    Identification Number: https://doi.org/10.3109/13693780903405782
    Depositing User: Dr. Kevin Kavanagh
    Date Deposited: 01 Oct 2019 13:34
    Journal or Publication Title: Medical Mycology
    Publisher: ISHAM (International Society for Human and Animal Mycology)
    Refereed: Yes
    Funders: Higher Education Authority (HEA)
    URI:

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