Malassezia yeasts produce a collection of exceptionally potent activators of the ah (dioxin) receptor detected in diseased human skin

Prokopios Magiatis, Periklis Pappas, George Gaitanis, Nikitia Mexia, Eleni Melliou, Maria Galanou, Christophoros Vlachos, Konstantina Stathopoulou, Alexios Leandros Skaltsounis, Marios Marselos, Aristea Velegraki, Michael S. Denison, Ioannis D. Bassukas

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Malassezia yeasts are commensal microorganisms, which under insufficiently understood conditions can become pathogenic. We have previously shown that specific strains isolated from diseased human skin can preferentially produce agonists of the aryl hydrocarbon receptor (AhR), whose activation has been linked to certain skin diseases. Investigation of skin scale extracts from patients with Malassezia-associated diseases demonstrated 10-to 1,000-fold higher AhR-activating capacity than control skin extracts. Liquid chromatography-tandem mass spectrometry analysis of the patients' extracts revealed the presence of indirubin, 6-formylindolo[3,2-b]carbazole (FICZ), indolo[3,2-b]carbazole (ICZ), malassezin, and pityriacitrin. The same compounds were also identified in 9 out of 12 Malassezia species culture extracts tested, connecting their presence in skin scales with this yeast. Studying the activity of the Malassezia culture extracts and pure metabolites in HaCaT cells by reverse transcriptase real-time PCR revealed significant alterations in mRNA levels of the endogenous AhR-responsive genes Cyp1A1, Cyp1B1, and AhRR. Indirubin-and FICZ-activated AhR in HaCaT and human HepG2 cells with significantly higher, yet transient, potency as compared with the prototypical AhR ligand, dioxin. In loco synthesis of these highly potent AhR inducers by Malassezia yeasts could have a significant impact on skin homeostatic mechanisms and disease development.

Original languageEnglish (US)
Pages (from-to)2023-2030
Number of pages8
JournalJournal of Investigative Dermatology
Volume133
Issue number8
DOIs
StatePublished - Aug 2013

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Malassezia yeasts produce a collection of exceptionally potent activators of the ah (dioxin) receptor detected in diseased human skin'. Together they form a unique fingerprint.

  • Cite this

    Magiatis, P., Pappas, P., Gaitanis, G., Mexia, N., Melliou, E., Galanou, M., Vlachos, C., Stathopoulou, K., Skaltsounis, A. L., Marselos, M., Velegraki, A., Denison, M. S., & Bassukas, I. D. (2013). Malassezia yeasts produce a collection of exceptionally potent activators of the ah (dioxin) receptor detected in diseased human skin. Journal of Investigative Dermatology, 133(8), 2023-2030. https://doi.org/10.1038/jid.2013.92