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    Assessment of the in vitro and in vivo activity of atorvastatin against Candida albicans


    Ajdidi, Ahmad and Sheehan, Gerard and Abu-Elteen, Khaled and Kavanagh, Kevin (2019) Assessment of the in vitro and in vivo activity of atorvastatin against Candida albicans. Journal of Medical Microbiology, 68. pp. 1497-1506. ISSN 0022-2615

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    Abstract

    Aim. The aim of this work was to characterize the response of Candida albicans to atorvastatin, and to assess its in vivo anti-fungal capability. Methodology. The effect of atorvastatin on the growth and viability of C. albicans was assessed. The ability of the statin to alter cell permeability was quantified by measuring amino acid and protein leakage. The response of C. albicans to atorvastatin was assessed using label-free quantitative proteomics. The in vivo antifungal activity of atorvastatin was assessed using Galleria mellonella larvae infected with C. albicans. Results. Atorvastatin inhibited the growth of C. albicans. The atorvastatin-treated cells showed lower ergosterol levels than the controls, demonstrated increased calcofluor staining and released elevated quantities of amino acids and protein. Larvae infected with C. albicans showed a survival rate of 18.1±4.2% at 144 h. In contrast, larvae administered atorvastatin (9.09 mg kg−1) displayed a survival rate of 60.2±6.4% (P<0.05). Label-free quantitative proteomics identified 1575 proteins with 2 or more peptides and 465 proteins were differentially abundant (P<0.05). There was an increase in the abundance of enzymes with oxidoreductase and hydrolase activity in atorvastatin-treated cells, and squalene monooxygenase (4.52-fold increase) and lanosterol synthase (2.84-fold increase) were increased in abundance. Proteins such as small heat shock protein 21 (−6.33-fold) and glutathione peroxidase (−2.05-fold) were reduced in abundance. Conclusion. The results presented here indicate that atorvastatin inhibits the growth of C. albicans and is capable of increasing the survival of G. mellonella larvae infected with C. albicans.

    Item Type: Article
    Keywords: atorvastatin; Candida; ergosterol; Galleria mellonella; infection; statin;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 14996
    Identification Number: https://doi.org/10.1099/jmm.0.001065
    Depositing User: Dr. Kevin Kavanagh
    Date Deposited: 08 Nov 2021 16:03
    Journal or Publication Title: Journal of Medical Microbiology
    Publisher: Society for General Microbiology
    Refereed: Yes
    URI:
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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