HIV-Protease inhibitors reduce cell adherence of Candida albicans strains by inhibition of yeast secreted aspartic proteases

Details

Serval ID
serval:BIB_D35C96E7B67C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
HIV-Protease inhibitors reduce cell adherence of Candida albicans strains by inhibition of yeast secreted aspartic proteases
Journal
Journal of Investigative Dermatology
Author(s)
Borg-von Zepelin  M., Meyer  I., Thomssen  R., Wurzner  R., Sanglard  D., Telenti  A., Monod  M.
ISSN
0022-202X (Print)
Publication state
Published
Issued date
11/1999
Volume
113
Number
5
Pages
747-51
Notes
Journal Article --- Old month value: Nov
Abstract
Since the introduction of new anti-retroviral agents such as human immunodeficiency virus (HIV) protease inhibitors, oropharyngeal candidiasis is less often observed in acquired immune deficiency syndrome patients. Secretory aspartic proteases of Candida albicans, which have similarities to the HIV aspartic proteases, are pathogenicity factors that have been intensively investigated in recent years. The inhibitory effect of four different HIV aspartic protease inhibitors (ritonavir, saquinavir, indinavir, and nelfinavir), on the activity of different Candida albicans secretory aspartic proteases was demonstrated. These anti-retroviral agents were able to inhibit Candida albicans secretory aspartic proteases 1, 2, and 3 which are involved in Candida adherence. As a consequence of these results we used selected HIV protease inhibitors in an adherence assay of Candida cells to epithelial cells. Ritonavir and saquinavir inhibited adherence of Candida albicans under the chosen experimental conditions similarly to the in vitro results, whereas indinavir had no effect. This inhibition was shown to be concentration dependent. The specificity of these effects with respect to the secretory aspartic proteases was demonstrated by competitive binding experiments using purified recombinant secretory aspartic proteases. On the basis of these studies we conclude that lower rates of oropharyngeal candidiasis in individuals receiving potent anti-retroviral therapy could reflect not only an improvement in the immune system but also direct inhibition of Candida secretory aspartic proteases by HIV protease inhibitors.
Keywords
Aspartic Endopeptidases/*antagonists & inhibitors/*secretion Candida albicans/*cytology/enzymology Cell Adhesion/drug effects HIV Protease Inhibitors/*pharmacology Humans Microscopy, Fluorescence Ritonavir/pharmacology Saquinavir/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 16:47
Last modification date
20/08/2019 15:53
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