HIV protease inhibitors attenuate adherence of Candida albicans to epithelial cells in vitro

Oropharyngeal candidiasis is one of the first and most commonly reported op portunistic infections of untreated AIDS patients. With the introduction of the new antiviral HAART therapy, including HIN protease inhibitors, this m ucocutaneous infection is nowadays only rarely observed in treated patients . It was recently shown that HIV protease inhibitors have a direct attenuat ing effect on Candida albicans secreted aspartic proteinases (Saps), an inv estigation prompted by the fact that both Sap and HIV protease belong to th e superfamily of aspartic proteinases and by the observation that mucocutan eous infections sometimes resolve even in the absence of an immunological i mprovement of the host. As these Saps are important fungal virulence factor s and play a key role in adhesion to human epithelial cells we tried to ass ess the effect of the HIV protease inhibitors Ritonavir, Indinavir and Saqu inavir on fungal adhesion to these cells. The effect on phagocytosis by pol ymorphonuclear leukocytes was also assessed. Ritonavir was found to be the most potent inhibitor of fungal adhesion. A dose-dependent inhibition of ad hesion to epithelial cells was found already at 0.8 muM and was significant at 4 muM or higher, at 500 muM the inhibition was about 55%. Indinavir and Saquinavir inhibited significantly at 4 muM or 20 muM, respectively; at 50 0 muM the inhibition was 30% or 50%. In contrast, no protease inhibitor was able to modulate phagocytosis of Candida by polymorphonuclear leukocytes. In conclusion, inhibition of Saps by HIV protease inhibitors may directly h elp to ease the resolution of mucosal candidiasis. In future, derivatives o f HIV protease inhibitors, being more specific for the fungal Saps, may for m an alternative in the treatment of mucosal candidiasis insensitive to cur rently available antimycotics. (C) 2001 Federation of European Microbiologi cal Societies. Published by Elsevier Science B.V. All rights reserved.