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Basidiomycete metabolites attenuate virulence properties of Candida albicans in vitro

Abstract number: 902_p546

Pleyer L.

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Objective:

The previously used stratagem of targeting a singular cellular metabolic or biosynthetic process in antifungal drug design has proven inadequate, especially with regard to the increasing drug-resistance. We therefore studied the recently discovered basidomycete protease inhibitors Aureoquinone and Laccaridiones A and B for their ability to block fungal adhesion and to inhibit candidial secreted aspartate protease (Sap) release.

Methods:

Inhibition of adhesion was tested on endothelial and epithelial cells, Sap antigen concentrations by specific ELISA and their activity by enzymatic cleavage of bovine serum albumin.

Results:

The inhibition of C. albicans adhesion to the epithelial cell line Hela S3 was shown to be dose dependant and highly significant (24% inhibition with Aureoquinone, 35% with Laccaridione A and 56% with Laccaridione B at 10 mg/mL, respectively), clearly marking Laccaridione B as the front runner. The inhibitory effect of Laccaridione B on candidial adherence to the endothelial cell line EAhy 926 was an even greater (highly significant 66%). Concerning Sap-release Laccaridione B also proved to be the most effective among the substances tested, showing a significant 50% reduction in concentration and a reduced activity at 10 mg/mL. The inhibitory effects observed were shown to be the result of an inhibition of Sap-production and/or -release and not due to a direct interaction of the basidiomycete metabolites with Sap. For both Sap-release and activity a single application of the drug resulted in a much less pronounced effect than regular drug addition over a period of 8 days.

Conclusion:

Animal studies will show whether Laccaridione A and especially Laccaridione B, or derivatives thereof, may also represent potent antifungal drugs in vivo targeting fungal virulence factors such as adhesion and protease release, without being fungicidal.

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Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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