title: AhR ligands, malassezin, and indolo[3,2-b]carbazole are selectively produced by Malassezia furfur strains isolated from seborrheic dermatitis.
abstract: Malassezia yeasts are connected with seborrheic dermatitis (SD) whereas M. furfur pathogenicity is associated with the production of bioactive indoles. In this study, the production of indoles by M. furfur isolates from healthy and diseased skin was compared, the respective HPLC patterns were analyzed, and substances that are preferentially synthesized by strains isolated from SD lesions were isolated and characterized. Malassezin, pityriacitrin, indole-3-carbaldehyde, and indolo[3,2-b]carbazole (ICZ) were isolated by HPLC from extracts of M. furfur grown in L-tryptophan agar, and identified by nuclear magnetic resonance and mass spectroscopy. Of these, ICZ, a potent ligand of the aryl hydrocarbon receptor (AhR), is described for the first time to our knowledge as a M. furfur metabolite. HPLC-photodiode array detection analysis of strain extracts from 7 healthy subjects and 10 SD patients showed that M. furfur isolates from only SD patients consistently produce malassezin and ICZ. This discriminatory production of AhR agonists provides initial evidence for a previously unreported mechanism triggering development of SD and indicates that the variable pathogenicity patterns recorded for M. furfur-associated SD conditions may be attributed to selective production (P<0.001) of measurable bioactive indoles.
authors.affiliation: Mycology Laboratory, Department of Microbiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Gaitanis
authors.forename: Prokopios
authors.initials: P
authors.lastname: Magiatis
authors.forename: Konstantina
authors.initials: K
authors.lastname: Stathopoulou
authors.forename: Ioannis D
authors.initials: ID
authors.lastname: Bassukas
authors.forename: Evangelos C
authors.initials: EC
authors.lastname: Alexopoulos
authors.forename: Aristea
authors.initials: A
authors.lastname: Velegraki
authors.forename: Alexios-Leandros
authors.initials: AL
authors.lastname: Skaltsounis
mesh_terms: D002227:Carbazoles / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D012628:Dermatitis, Seborrheic / Q000382:microbiology*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008290:Malassezia / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D012867:Skin / Q000382:microbiology*
chemical_list: D002227:Carbazoles; D007211:Indoles; D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon; C436511:malassezin; C075954:indolo(3,2-b)carbazole