Fungi on the Skin: Dermatophytes and Malassezia

Skin fungi are associated with many of humanity’s most common disorders, including dandruff, atopic dermatitis/eczema, ringworm, athlete’s foot, jock itch, and nail infections (onychomycosis). These diseases are attributed to two sets of fungi, ascomycete dermatophytes, including the genera Trichophyton, Microsporum, and Epidermophyton, and basidiomycete fungi in the genus Malassezia. Research on dermatophytes and Malassezia has lagged behind research on fungi associated with human mortality, although most of the world’s people constantly deal with fungal skin disease, whether acute or chronic. Genome sequencing has led to new hypotheses for the molecular means by which these fungi inhabit human skin and cause disease. Not only are these two sets of skin fungi from distant branches of the fungal phylogenetic tree (Fig. 1), but they also use different sets of proteins to adapt to mammalian skin (Table 1). The dermatophytes appear to use a plethora of proteases to devour keratin, LysM proteins to hide from the host immune system, kinases and pseudokinases to modulate cell metabolism, and a wealth of polyketide synthases and nonribosomal peptide synthases to generate metabolites for unknown purposes. Malassezia are found on the skin of warm-blooded animals and are the most numerous fungus on many human skin sites. Their phylogenetically closest relatives are plant pathogens such as Ustilago maydis (Fig. 1), but Malassezia secrete a set of proteins with activities similar to secreted proteins of another skin-inhabiting fungus, Candida albicans. Most Malassezia species are unable to synthesize fatty acids, a deficiency not known in other free-living fungi. Malassezia compensate by using many secreted hydrolases (lipases and phopholipases C) to provide fatty acids from host lipids. Figure 1. Phylogenetic relationship of dermatophytes and Malassezia to other fungi. The phylogenetic relationship of selected fungi was estimated from 616 single-copy orthologs present in all species; protein sequences were aligned using MUSCLE (Edgar 2004), and ... Table 1. Significant observations from the dermatophyte and Malassezia genomes Other skin fungi are responsible for emerging diseases that are altering the biosphere. Many amphibian species are threatened with extinction, and a chytrid fungus, growing on frog skin, may be primarily responsible (Cheng et al. 2011). More recently, bat populations have plummeted because of a Geomyces fungal infection of bats, which colonizes the facial and wing skin (Blehert et al. 2009). Although these wildlife-killing fungi will not be covered in this review, understanding of one skin fungal pathogen may lead to hypotheses relevant to others. We will describe the dermatophytes and Malassezia, along with some of the diseases with which they are associated. We will provide a perspective on the phylogeny, ecology, and genomics of these organisms.