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Antimicrobial Agents and Chemotherapy, January 2004, p. 41-47, Vol. 48, No. 1
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.1.41-47.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Effects of Aspirin and Other Nonsteroidal Anti-Inflammatory Drugs on Biofilms and Planktonic Cells of Candida albicans

Mohammed A. S. Alem and L. Julia Douglas*

Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom

Received 8 September 2003/ Returned for modification 24 September 2003/ Accepted 3 October 2003

Prostaglandins are now known to be produced by Candida albicans and may play an important role in fungal colonization. Their synthesis in mammalian cells is decreased by inhibitors of the cyclooxygenase isoenzymes required for prostaglandin formation. In the present study, a catheter disk model system was used to investigate the effects of nonsteroidal anti-inflammatory drugs (all cyclooxygenase inhibitors) on biofilm formation by three strains of C. albicans. Seven of nine drugs tested at a concentration of 1 mM inhibited biofilm formation. Aspirin, etodolac, and diclofenac produced the greatest effects, with aspirin causing up to 95% inhibition. Celecoxib, nimesulide, ibuprofen, and meloxicam also inhibited biofilm formation, but to a lesser extent. Aspirin was active against growing and fully mature (48-h) biofilms; its effect was dose related, and it produced significant inhibition (20 to 80%) at pharmacological concentrations. Simultaneous addition of prostaglandin E2 abolished the inhibitory effect of 25 or 50 µM aspirin. At 1 mM, aspirin reduced the viability of biofilm organisms to 1.9% of that of controls. Surviving cells had a wrinkled appearance, as judged by scanning electron microscopy, and consisted of both yeasts and hyphae. Treatment with other cyclooxygenase inhibitors, such as etodolac, resulted in biofilms that consisted almost entirely of yeast cells. In conventional assays for germ tube formation, these drugs produced significant inhibition, whereas aspirin had little effect. Our findings suggest that cyclooxygenase-dependent synthesis of fungal prostaglandin(s) is important for both biofilm development and morphogenesis in C. albicans and may act as a regulator in these physiological processes. Our results also demonstrate that aspirin possesses potent antibiofilm activity in vitro and could be useful in combined therapy with conventional antifungal agents in the management of some biofilm-associated Candida infections.


* Corresponding author. Mailing address: Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom. Phone: 44 141 330 5842. Fax: 44 141 330 4600. E-mail: J.Douglas{at}bio.gla.ac.uk.


Antimicrobial Agents and Chemotherapy, January 2004, p. 41-47, Vol. 48, No. 1
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.1.41-47.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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