Genomic Insights into the Atopic Eczema-Associated Skin Commensal Yeast <italic toggle="yes">Malassezia sympodialis</italic>
Anastasia Gioti,
Björn Nystedt,
Wenjun Li,
Jun Xu,
Anna Andersson,
Anna F. Averette,
Karin Münch,
Xuying Wang,
Catharine Kappauf,
Joanne M. Kingsbury,
Bart Kraak,
Louise A. Walker,
Henrik J. Johansson,
Tina Holm,
Janne Lehtiö,
Jason E. Stajich,
Piotr Mieczkowski,
Regine Kahmann,
John C. Kennell,
Maria E. Cardenas,
Joakim Lundeberg,
Charles W. Saunders,
Teun Boekhout,
Thomas L. Dawson,
Carol A. Munro,
Piet W. J. de Groot,
Geraldine Butler,
Joseph Heitman,
Annika Scheynius
Affiliations
Anastasia Gioti
Science for Life Laboratory, Translational Immunology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
Björn Nystedt
Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
Wenjun Li
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA
Jun Xu
Procter & Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio, USA
Anna Andersson
Translational Immunology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
Anna F. Averette
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA
Karin Münch
Max Planck Institute for Terrestrial Microbiology, Marburg, Germany
Xuying Wang
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA
Catharine Kappauf
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA
Joanne M. Kingsbury
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA
Bart Kraak
CBS-Fungal Biodiversity Centre, Utrecht, The Netherlands
Louise A. Walker
Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
Henrik J. Johansson
Cancer Proteomics Mass Spectrometry, Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
Tina Holm
Translational Immunology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
Janne Lehtiö
Cancer Proteomics Mass Spectrometry, Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
Jason E. Stajich
Department of Plant Pathology & Microbiology University of California, Riverside, California, USA
Piotr Mieczkowski
Department of Genetics, Carolina Center for Genome Science, School of Medicine, University of North Carolina, at Chapel Hill, Chapel Hill, North Carolina, USA
Regine Kahmann
Max Planck Institute for Terrestrial Microbiology, Marburg, Germany
John C. Kennell
Department of Biology, Saint Louis University, St. Louis, Missouri, USA
Maria E. Cardenas
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA
Joakim Lundeberg
Science for Life Laboratory School of Biotechnology, Division of Gene Technology, Royal Institute of Technology, Stockholm, Sweden
Charles W. Saunders
Procter & Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio, USA
Teun Boekhout
CBS-Fungal Biodiversity Centre, Utrecht, The Netherlands
Thomas L. Dawson
Procter & Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio, USA
Carol A. Munro
Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
Piet W. J. de Groot
Regional Center for Biomedical Research, Albacete Science & Technology Park, University of Castilla-La Mancha, Albacete, Spain
Geraldine Butler
School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
Joseph Heitman
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA
Annika Scheynius
Translational Immunology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
ABSTRACT Malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. Here we describe the 7.67-Mbp genome of Malassezia sympodialis, a species associated with atopic eczema, and contrast its genome repertoire with that of Malassezia globosa, associated with dandruff, as well as those of other closely related fungi. Ninety percent of the predicted M. sympodialis protein coding genes were experimentally verified by mass spectrometry at the protein level. We identified a relatively limited number of genes related to lipid biosynthesis, and both species lack the fatty acid synthase gene, in line with the known requirement of these yeasts to assimilate lipids from the host. Malassezia species do not appear to have many cell wall-localized glycosylphosphatidylinositol (GPI) proteins and lack other cell wall proteins previously identified in other fungi. This is surprising given that in other fungi these proteins have been shown to mediate interactions (e.g., adhesion and biofilm formation) with the host. The genome revealed a complex evolutionary history for an allergen of unknown function, Mala s 7, shown to be encoded by a member of an amplified gene family of secreted proteins. Based on genetic and biochemical studies with the basidiomycete human fungal pathogen Cryptococcus neoformans, we characterized the allergen Mala s 6 as the cytoplasmic cyclophilin A. We further present evidence that M. sympodialis may have the capacity to undergo sexual reproduction and present a model for a pseudobipolar mating system that allows limited recombination between two linked MAT loci. IMPORTANCE Malassezia commensal yeasts are associated with a number of skin disorders. The previously published genome of M. globosa provided some of the first insights into Malassezia biology and its involvement in dandruff. Here, we present the genome of M. sympodialis, frequently isolated from patients with atopic eczema and healthy individuals. We combined comparative genomics with sequencing and functional characterization of specific genes in a population of clinical isolates and in closely related model systems. Our analyses provide insights into the evolution of allergens related to atopic eczema and the evolutionary trajectory of the machinery for sexual reproduction and meiosis. We hypothesize that M. sympodialis may undergo sexual reproduction, which has important implications for the understanding of the life cycle and virulence potential of this medically important yeast. Our findings provide a foundation for the development of genetic and genomic tools to elucidate host-microbe interactions that occur on the skin and to identify potential therapeutic targets.