title: Comparative genome analysis of Trichophyton rubrum and related dermatophytes reveals candidate genes involved in infection.
abstract: The major cause of athlete's foot is Trichophyton rubrum, a dermatophyte or fungal pathogen of human skin. To facilitate molecular analyses of the dermatophytes, we sequenced T. rubrum and four related species, Trichophyton tonsurans, Trichophyton equinum, Microsporum canis, and Microsporum gypseum. These species differ in host range, mating, and disease progression. The dermatophyte genomes are highly colinear yet contain gene family expansions not found in other human-associated fungi. Dermatophyte genomes are enriched for gene families containing the LysM domain, which binds chitin and potentially related carbohydrates. These LysM domains differ in sequence from those in other species in regions of the peptide that could affect substrate binding. The dermatophytes also encode novel sets of fungus-specific kinases with unknown specificity, including nonfunctional pseudokinases, which may inhibit phosphorylation by competing for kinase sites within substrates, acting as allosteric effectors, or acting as scaffolds for signaling. The dermatophytes are also enriched for a large number of enzymes that synthesize secondary metabolites, including dermatophyte-specific genes that could synthesize novel compounds. Finally, dermatophytes are enriched in several classes of proteases that are necessary for fungal growth and nutrient acquisition on keratinized tissues. Despite differences in mating ability, genes involved in mating and meiosis are conserved across species, suggesting the possibility of cryptic mating in species where it has not been previously detected. These genome analyses identify gene families that are important to our understanding of how dermatophytes cause chronic infections, how they interact with epithelial cells, and how they respond to the host immune response.
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Martinez
authors.forename: Brian G
authors.initials: BG
authors.lastname: Oliver
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Gräser
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Goldberg
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.forename: Nilce M
authors.initials: NM
authors.lastname: Martinez-Rossi
authors.forename: Michel
authors.initials: M
authors.lastname: Monod
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shelest
authors.forename: Richard C
authors.initials: RC
authors.lastname: Barton
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Birch
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
authors.forename: Zehua
authors.initials: Z
authors.lastname: Chen
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Gurr
authors.forename: David
authors.initials: D
authors.lastname: Heiman
authors.forename: Joseph
authors.initials: J
authors.lastname: Heitman
authors.forename: Idit
authors.initials: I
authors.lastname: Kosti
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.forename: Sakina
authors.initials: S
authors.lastname: Saif
authors.forename: Marketa
authors.initials: M
authors.lastname: Samalova
authors.forename: Charles W
authors.initials: CW
authors.lastname: Saunders
authors.forename: Terrance
authors.initials: T
authors.lastname: Shea
authors.forename: Richard C
authors.initials: RC
authors.lastname: Summerbell
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Sarah
authors.initials: S
authors.lastname: Young
authors.forename: Qiandong
authors.initials: Q
authors.lastname: Zeng
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Birren
authors.forename: Christina A
authors.initials: CA
authors.lastname: Cuomo
authors.forename: Theodore C
authors.initials: TC
authors.lastname: White
mesh_terms: D003883:Arthrodermataceae / Q000235:genetics* / Q000472:pathogenicity*; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D005800:Genes, Fungal; D016681:Genome, Fungal; D006801:Humans; D008864:Microsporum / Q000235:genetics* / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D014249:Trichophyton / Q000235:genetics* / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D004271:DNA, Fungal; D037521:Virulence Factors