title: Basidiomycete metabolites attenuate virulence properties of Candida albicans in vitro.
abstract: Secreted aspartic proteases (Saps) represent an important virulence factor facilitating fungal adherence. Several protease inhibitors (PIs), including HIV PIs, have been shown to reduce Candida adhesion. The aim of this study was to ascertain whether or not the recently discovered PIs Aureoquinone and Laccaridiones A and B, isolated from Basidiomycete cultures, or Bestatin, act as Sap-inhibitors and/or inhibitors of fungal adhesion. Drug effects on candidial Sap-production were determined by Sap-ELISA. Control tubes, in the absence of drug, served as positive controls, while tubes excluding both drug and proteinase induction medium were used as negative controls. Aureoquinone as well as Laccaridiones A and B, but not Bestatin, significantly inhibited Candida albicans adhesion to both epithelial and endothelial cells in a dose dependent manner and also reduced Sap-release (effects were not because of a direct interaction of the Basidiomycete metabolites with secreted Saps). Laccaridione B was consistently found to be the most effective PI tested. Interestingly, these drugs are neither fungistatic nor fungicidal at the concentrations applied. Laccaridione B may represent a promising novel type of antimycotic drug--targeting virulence factors without killing the yeast.
authors.affiliation: Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Falkensammer
authors.forename: Lisa
authors.initials: L
authors.lastname: Pleyer
authors.forename: Sigrun
authors.initials: S
authors.lastname: Ressler
authors.forename: Albrecht
authors.initials: A
authors.lastname: Berg
authors.forename: Margarethe
authors.initials: M
authors.lastname: Borg-von Zepelin
authors.forename: Markus
authors.initials: M
authors.lastname: Nagl
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lass-Flörl
authors.forename: Cornelia
authors.initials: C
authors.lastname: Speth
authors.forename: Manfred P
authors.initials: MP
authors.lastname: Dierich
authors.forename: Reinhard
authors.initials: R
authors.lastname: Würzner
mesh_terms: D000898:Antibiosis; D001487:Basidiomycota / Q000378:metabolism*; D016227:Benzoquinones / Q000378:metabolism; D002176:Candida albicans / Q000254:growth & development / Q000472:pathogenicity*; D002448:Cell Adhesion; D002460:Cell Line; D042783:Endothelial Cells / Q000382:microbiology; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology*; D011809:Quinones / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D011480:Protease Inhibitors; D011809:Quinones; C420728:aureoquinone; C420731:laccaridione B; D007930:Leucine; C012211:ubenimex; C420730:laccaridione A