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    Erythromycin, an inhibitor of mitoribosomal protein biosynthesis, alters the amphotericin B susceptibility of Candida albicans

    Geraghty, Patrick and Kavanagh, Kevin (2003) Erythromycin, an inhibitor of mitoribosomal protein biosynthesis, alters the amphotericin B susceptibility of Candida albicans. Journal of Pharmacy and Pharmacology, 55 (2). pp. 179-184.

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    Exposure of the yeast Candida albicans to the macrolide antibiotic erythromycin (C37H67NO13) results in elevated tolerance to the polyene antifungal amphotericin e. Erythromycin displays no fungistatic activity against C. albicans but inhibits the synthesis of cytochromes, particularly cytochrome aa(3). Consequently there is a reduction in aerobic respiration by up to 90% when cells are exposed to 10 mg mL(-1) erythromycin. Cellular ergosterol levels are also severely reduced. Erythromycin inhibits protein biosynthesis in ribosomes (mitoribosomes) located within the mitochondrion of the yeast cell, which results in a disruption of cytochrome biosynthesis with an adverse effect on respiration. The synthesis of ergosterol is oxygen dependent and consequently ergosterol levels are depleted in erythromycin-treated C. albicans. Ergosterol is the target for amphotericin B and since there is less of this sterol in erythromycin-treated cells, there is an increase in tolerance of the antifungal agent. Our work indicates that co- administration of erythromycin and amphotericin B to control bacterial and fungal infections, respectively, may inadvertently lead to an elevation in the tolerance of C. albicans for this antifungal agent.

    Item Type: Article
    Keywords: Antifungal susceptibility; IN-VITRO; Fluconzole; Dubliniensis; Resistance; Infections; Therapy;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 180
    Depositing User: Dr. Kevin Kavanagh
    Date Deposited: 10 Jan 2005
    Journal or Publication Title: Journal of Pharmacy and Pharmacology
    Publisher: Royal Pharmaceutical Society Great Britain
    Refereed: Yes
      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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