An Aspirin A Day Keeps the Biofilm at Bay
Abstract & Commentary
Synopsis: Aspirin possesses potent activity against the formation of biofilms formed by Candida albicans and could be useful in combination for managing biofilm-associated infections.
Source: Alem MAS. Effects of aspirin and other nonsteroidal anti-inflammatory drugs on biofilms and planktonic cells of Candida albicans. Antimicrob Ag Chemother. 2004;48:41-47.
Pathogenic fungi including the yeast Candida albicans produce prostaglandins that may modulate host immune responses but also assist virulence by enhancing germ-tube formation. Inhibitors of cyclooxygenase (COX) isoenzymes (eg, ibuprofen) also inhibit fungal prostaglandin synthesis. This is manifest in C albicans by loss of biofilm production and less hyphae formation Alem and colleagues explored this phenomenon further by exposing 3 strains of C albicans to aspirin and a variety of other NSAIDS (diclofenac, ibuprofen, indomethacin, meloxicam, piroxicam, etodolac, celecoxib, and nimesulide) and showed aspirin to be very effective in preventing biofilm formation at concentrtions of 100 µM or more (= 18 mg/L)—more so than the other NSAIDs (see Figure, below)—and at concentrations that are attainable in blood after a regular dose of 500-1000 mg.
| Figure |
| The Effect of Asprin and Other NSAIDS on Biofilm Formation of Candida albicans |
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Aspirin did not simply inhibit biofilm formation since it had little effect on adhesion but inhibited the metabolic activity of yeasts already embedded in established biofilm. The effect could be reversed by adding prostaglandin E2. Aspirin also drastically reduced the viability of the biofilm to 1%, whereas other COX inhibitors were much less effective, with indomethacin having no effect at all. The cell surfaces of the yeast appeared wrinkled after exposure to aspirin, but not the other drugs, indicating that aspirin exerts damage in several different ways. The NSAIDs could be divided into 2 groups in terms of their effect on biofilm. Both yeast cells and hyphal forms were apparent after exposure to piroxicam and aspirin, whereas exposure to etodolac and indomethacin resulted in biofilms consisting almost entirely of yeast cells. The effect of each drug on germ-tube formation was examined specifically and showed that aspirin had almost no effect, while ibuprofen, indomethacin, and celecoxib resulted in 80% fewer germ tubes when compared with untreated controls. Alem et al concluded that the effects of NSAIDS on the development of biofilms and morphogenesis of C albicans suggest that these processes involve COX-dependent synthesis of fungal prostaglandins, opening up therapeutic possibilities for managing biofilm-associated infections, particularly with aspirin.
Comment by J. Peter Donnelly, PhD
Biofilms are now accepted as the typical mode of growth for many, if not most, bacteria and yeasts associated with infections on natural and artificial surfaces, be it mucous membranes or catheters and implants. Unlike planktonic cells, cells in biofilm consortia are more resistant to biocides, antiseptics, and antibiotics, making prevention and treatment difficult, if not impossible. The recalcitrant nature of implant infections with C albicans such as those affecting central venous catheters in patients for whom they are fairly essential is frustrating, with removal of the device being the only effective option. This makes the observations reported in this article all the more interesting, especially as the NSAIDS are readily available and familiar drugs. Exploring aspirin further for its efficacy in preventing colonization of devices is an obvious point of departure. This might be achieved by instillation or using the so-called "lock" technique whereby the drug is left in contact with the lumen surfaces of the device for several minutes as has been done with antibiotics. The apparent activity of aspirin against bacteria like the staphylococci commonly involved in these infections makes this even more attractive. Just as interesting is the observation that other NSAIDS like ibuprofen, indomethacin, and celecoxib inhibit germ-tube formation, which is a prelude to infection on body surfaces including the oral cavity and vagina. This may open up alternative avenues for patients suffering chronic infections of these sites. Most intriguingly of all, these apparently off-beat laboratory studies serve to remind us to look beyond the obvious and explore the effects of agents that are not primarily antimicrobial but nonetheless influence the physiology of pathogenic microorganisms and help shift the balance in favor of the host.
Suggested Reading
1. Bouza E, et al. Catheter-related infections: Diagnosis and intravascular treatment. Clin Microbiol Infect. 2002;8:265-274.
Peter J. Donnely, PhD, Clinical Microbiologist, University Hospital, Nijmegen, The Netherlands, Section Editor Microbiology, is Associate Editor for Infectious Disease Alert.
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