Basidiomycete metabolites attenuate virulence properties of Candida albicans in vitro
Abstract number: 902_p546
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.
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.
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.
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."
|Session name:||XXIst ISTH Congress|
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