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.

The Malassezia Genus in Skin and Systemic Diseases

“…However, conventional culture and identification methods offer the advantage of further evaluating the isolates for possible virulence factors, such as the production of phospholipase (44,170) and indole (108,184,336) and melanin synthesis (107). Furthermore, this was highlighted in a study by Akaza et al (6), in which the seasonal rates of isolation of Malassezia species from healthy skin determined by quantitative PCR (qPCR) were compared with those determined by use of Leeming-Notman agar (197).…”

“…This also accelerated developments in PCR-based identification methods (Table 2), promoted investigation into Malassezia epidemiology (64,112) and pathobiology (108), and encouraged re-search on the association of certain Malassezia species with specific geographical locations (136).…”

“…Thus, the ability of Malassezia to locally modify the immune response, in addition to host susceptibility and the production of secondary metabolites by the yeast, probably participates in eliciting and maintaining seborrheic dermatitis. Higher production rates of aryl hydrocarbon receptor (AhR) ligands in vitro by M. furfur have been associated with seborrheic dermatitis isolates (108). AhR is found in sebocytes (169), and its function is modified by epidermal growth factor receptor (EGFR) (268,301).…”

Mycobiota: Micro-Eukaryotes Inhabiting Our Body as Commensals or Opportunistic Pathogens

“…In addition to the evidence that via AhR activation Lactobacillus reuteri, contributes to mucosal resistance against the opportunistic pathogen Candida. albicans [43], an increased concentration of AhR ligands in the skin has been linked to the development of Malassezia-associated skin diseases [44,45].…”

Fungi on the Skin: Dermatophytes and Malassezia

“…These indoles (malassezin, indolo[3,2-b] carbazole, pityriacitrin, and indirubin) were found in extracts of skin from SD and PV patients but not in healthy controls (Magiatis et al 2013). The first three of these materials were produced by M. furfur strains isolated from SD patients when these strains were cultivated in L-tryptophan agar (Gaitanis et al 2008). Control strains from healthy patients grew poorly and produced lower amounts of indoles.…”