Genomic Insights into the Atopic Eczema-Associated Skin Commensal Yeast Malassezia sympodialis

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.

Evolution of Mating Systems in Basidiomycetes and the Genetic Architecture Underlying Mating-Type Determination in the YeastLeucosporidium scottii

“…In addition to promoting genetic variation, required for adaptation to fluctuating environments and longterm survival, sexual reproduction in many fungal species, in particular, has a central role in pathogenic development (Bakkeren et al 2008;Nadal et al 2008;Heitman 2010;Heitman et al 2014). It is thus not surprising that recent advances in genome sequencing have revealed that most fungal species have retained the machinery for sexual reproduction and meiosis (Halary et al 2011;Dyer and O'Gorman 2012;Gioti et al 2013;Heitman et al 2014). However, this resilience to keep sexual competence intact comes with an extremely dynamic evolution of sexual behaviors and mating type-determining mechanisms, which may influence important evolutionary and ecological processes, such as adaptation and speciation (Billiard et al 2011;Heitman et al 2013;Nieuwenhuis et al 2013).…”

Evolutionary Perspectives on Human Fungal Pathogens

“…Also in Basidiomycota, genomes of the agent of atopic eczema, Malassezia sympodialis and that associated with dandruff, Malassezia globosa, have been compared with the expected finding in these lipophilic yeasts of no genes for fatty acid synthesis and few genes for lipid biosynthesis, and the unexpected result that there were few genes known to mediate adhesion or biofilm production in organisms that seemingly must adhere to their hosts (Gioti et al 2013). Given the role that fungi must play in allergies, an exciting aspect of the study was a focus on antigenic proteins, one of which, Mala S 7, has history of gene expansion.…”

Fungi on the Skin: Dermatophytes and Malassezia

“…Allergen-specific IgE against Malassezia can also be detected in children associated with their AD severity in infancy (Kekki et al 2013). Thirteen allergens have so far been identified in Malassezia (Scheynius and Crameri 2010), and at least 12 genes encoding different classes of the proteins have been confirmed to be present in both the M. sympodialis and M. globosa genomes (Gioti et al 2013). Interestingly, several of the identified allergens are proteins of unknown function with no sequence homology to characterized proteins, whereas others are homologous to host proteins, suggesting the possibility of cross-reactive immune responses.…”

“…There are several indications that Malassezia may be sexual. A mating locus has been found in all three Malassezia genome sequences that have been reported; a population study of M. sympodialis has provided evidence for recombination; and many meiosis and mating signaling genes are present (Gioti et al 2013). However, despite repeated attempts, no one has yet demonstrated mating in Malassezia (Gioti et al 2013).…”

“…Genome sequences from M. globosa, M. restricta (Xu et al 2007), and M. sympodialis (Gioti et al 2013) have provided insights into hypotheses for virulence and survival on host skin. These fungi are the only known free-living fungi to lack fatty acid synthase (Xu et al 2007), suggesting that they obtain lipids from the host skin.…”