title: Steroid toxicity and detoxification in ascomycetous fungi.
abstract: In the last couple of decades fungal infections have become a significant clinical problem. A major interest into fungal steroid action has been provoked since research has proven that steroid hormones are toxic to fungi and affect the host/fungus relationship. Steroid hormones were found to differ in their antifungal activity in ascomycetous fungi Hortaea werneckii, Saccharomyces cerevisiae and Aspergillus oryzae. Dehydroepiandrosterone was shown to be the strongest inhibitor of growth in all three varieties of fungi followed by androstenedione and testosterone. For their protection, fungi use several mechanisms to lower the toxic effects of steroids. The efficiency of biotransformation in detoxification depended on the microorganism and steroid substrate used. Biotransformation was a relatively slow process as it also depended on the growth phase of the fungus. In addition to biotransformation, steroid extrusion out of the cells contributed to the lowering of the active intracellular steroid concentration. Plasma membrane Pdr5 transporter was found to be the most effective, followed by Snq2 transporter and vacuolar transporters Ybt1 and Ycf1. Proteins Aus1 and Dan1 were not found to be involved in steroid import. The research of possible targets of steroid hormone action in fungi suggests that steroid hormones inhibit ergosterol biosynthesis in S. cerevisiae and H. werneckii. Results of this inhibition caused changes in the sterol content of the cellular membrane. The presence of steroid hormones most probably causes the degradation of the Tat2 permease and impairment of tryptophan import.
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Damjana
authors.initials: D
authors.lastname: Cvelbar
authors.forename: Vanja
authors.initials: V
authors.lastname: Zist
authors.forename: Katja
authors.initials: K
authors.lastname: Kobal
authors.forename: Dušan
authors.initials: D
authors.lastname: Zigon
authors.forename: Marija
authors.initials: M
authors.lastname: Zakelj-Mavrič
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism / Q000494:pharmacology; D001236:Aspergillus oryzae / Q000187:drug effects / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D001711:Biotransformation / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000378:metabolism / Q000494:pharmacology; D004875:Ergosterol / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects* / Q000378:metabolism*; D008658:Inactivation, Metabolic; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013261:Sterols / Q000493:pharmacokinetics* / Q000633:toxicity*; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology
chemical_list: D018528:ATP-Binding Cassette Transporters; C092438:PDR5 protein, S cerevisiae; C101797:SNQ2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols; C106609:YBT1 protein, S cerevisiae; C089179:YCF1 protein, S cerevisiae; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D004875:Ergosterol