title: Preliminary study of activity of the thioredoxin inhibitor pleurotin against Trichophyton mentagrophytes: a novel anti-dermatophyte possibility.
abstract: Dermatophyte infections, while not life-threatening, are very common, and there is great interest in developing new antifungal agents. Transcriptional profiling of Trichophyton on keratin has identified some antioxidant genes as induced on this host substrate, including a thioredoxin gene TmTRX1. If thioredoxin is a virulence factor, or necessary for the growth on keratin, thioredoxin inhibitors should act as antifungals. As a first evaluation of this hypothesis, we have tested the activity of a thioredoxin-inhibitory natural product, pleurotin, against a clinical isolate of each of two fungal pathogens: the dermatophyte T. mentagrophytes and Candida albicans. Pleurotin inhibited the growth of the dermatophyte in vitro and in an ex vivo skin model, but had no effect on Candida. It may be possible to develop and optimise thioredoxin inhibitors, some of which are already under study in cancer chemotherapy, as antifungals.
authors.affiliation: Department of Molecular Microbiology, Faculty of Medicine, Technion, Haifa, Israel. israelab@techunix.technion.ac.il
authors.forename: Israela
authors.initials: I
authors.lastname: Berdicevsky
authors.forename: Gil
authors.initials: G
authors.lastname: Kaufman
authors.forename: David J
authors.initials: DJ
authors.lastname: Newman
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Horwitz
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D004353:Drug Evaluation, Preclinical; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D012867:Skin / Q000382:microbiology; D013879:Thioredoxins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014005:Tinea / Q000382:microbiology*; D014249:Trichophyton / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D006576:Heterocyclic Compounds, 4 or More Rings; D013879:Thioredoxins; C479485:pleurotin