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

Abstract

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 E 2 abolished the inhibitory effect of 25 or 50 M 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.

The assessment of the antibacterial and antifungal activities of aspirin, EDTA and aspirin-EDTA combination and their effectiveness as antibiofilm agents

“…Nevertheless, it could be used in vitro and in situ, such as for catheter lock and flush solutions, if an appropriate concentration could be maintained. In vitro assessment of aspirin's antibiofilm activities was limited to two studies addressing different Candida species (Alem and Douglas 2004;Stepanovic et al 2004). The present study is the first to demonstrate the activity of aspirin against the established biofilms of E. coli and P. aeruginosa.…”

“…These effects include changes in membrane potentials and virulence factors production, reduction in extracellular polysaccharide and prostaglandin production (Price et al 2000;Wang et al 2003;Alem and Douglas 2004). These effects contribute to aspirin's antimicrobial activities against planktonic and biofilm cultures.…”

“…Nevertheless, both agents were reported to possess a weak and broad-spectrum antimicrobial activity towards some planktonic and biofilm cultures (Root et al 1988;Gil et al 1994;Nicolau et al 1995;Raad et al 2003;Alem and Douglas 2004;Stepanovic et al 2004;Percival et al 2005;Banin et al 2006;Yakandawala et al 2007).…”

Synthesis, characterization, and in vitro antimicrobial activity of organotin(IV) complexes with triazolo-pyrimidine ligands containing exocyclic oxygen atoms

“…albicans ATCC 10231 was cultivated in yeast nitrogen base (YNB) medium (Sigma) with 50 mM glucose at 37°C for 24 h. After this time it was diluted in the same medium to an optical density of 0.8 at 520 nm. [9]. 100 lL of such suspension were inoculated in wells of a 96-well plates at 37°C; after 24 h the wells were washed three times with 200 lL of sterile phosphate-buffered saline (PBS).…”

Eumicetoma: actualidades y perspectivas

“…En relación a esta observación clínica, encontramos que estudios in vitro e in vivo demostraron que otros AINE, como el ibuprofeno, potencian la actividad fungistáti-ca de los azoles; aunque el mecanismo de acción se desconoce por el momento, se considera que podría estar asociado con el efecto inhibidor del ibuprofeno sobre las bombas de transporte dependientes de ATP, mismas que se asocian a la resistencia fúngica 64 . Por otra parte, estudios en Candida albicans demostraron que los AINE disminuyen la formación de biofilms, lo que favorece el acceso de los medicamentos al hongo 65 . Además, en osteomielitis de origen bacteriano los AINE disminuyen el efecto citotóxico bacteriano sobre los osteoblastos 66 .…”