Comparative Genome Analysis of <italic toggle="yes">Trichophyton rubrum</italic> 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...

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Autores principales: Diego A. Martinez, Brian G. Oliver, Yvonne Gräser, Jonathan M. Goldberg, Wenjun Li, Nilce M. Martinez-Rossi, Michel Monod, Ekaterina Shelest, Richard C. Barton, Elizabeth Birch, Axel A. Brakhage, Zehua Chen, Sarah J. Gurr, David Heiman, Joseph Heitman, Idit Kosti, Antonio Rossi, Sakina Saif, Marketa Samalova, Charles W. Saunders, Terrance Shea, Richard C. Summerbell, Jun Xu, Sarah Young, Qiandong Zeng, Bruce W. Birren, Christina A. Cuomo, Theodore C. White
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Publicado: American Society for Microbiology 2012
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spelling oai:doaj.org-article:e9ff1081a0424d49a5ec7400f55e67022021-11-15T15:39:12ZComparative Genome Analysis of <italic toggle="yes">Trichophyton rubrum</italic> and Related Dermatophytes Reveals Candidate Genes Involved in Infection10.1128/mBio.00259-122150-7511https://doaj.org/article/e9ff1081a0424d49a5ec7400f55e67022012-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00259-12https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Athlete’s foot, jock itch, ringworm, and nail infections are common fungal infections, all caused by fungi known as dermatophytes (fungi that infect skin). This report presents the genome sequences of Trichophyton rubrum, the most frequent cause of athlete’s foot, as well as four other common dermatophytes. Dermatophyte genomes are enriched for four gene classes that may contribute to the ability of these fungi to cause disease. These include (i) proteases secreted to degrade skin; (ii) kinases, including pseudokinases, that are involved in signaling necessary for adapting to skin; (iii) secondary metabolites, compounds that act as toxins or signals in the interactions between fungus and host; and (iv) a class of proteins (LysM) that appear to bind and mask cell wall components and carbohydrates, thus avoiding the host’s immune response to the fungi. These genome sequences provide a strong foundation for future work in understanding how dermatophytes cause disease.Diego A. MartinezBrian G. OliverYvonne GräserJonathan M. GoldbergWenjun LiNilce M. Martinez-RossiMichel MonodEkaterina ShelestRichard C. BartonElizabeth BirchAxel A. BrakhageZehua ChenSarah J. GurrDavid HeimanJoseph HeitmanIdit KostiAntonio RossiSakina SaifMarketa SamalovaCharles W. SaundersTerrance SheaRichard C. SummerbellJun XuSarah YoungQiandong ZengBruce W. BirrenChristina A. CuomoTheodore C. WhiteAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 3, Iss 5 (2012)
institution DOAJ
collection DOAJ
language EN
topic Microbiology
QR1-502
spellingShingle Microbiology
QR1-502
Diego A. Martinez
Brian G. Oliver
Yvonne Gräser
Jonathan M. Goldberg
Wenjun Li
Nilce M. Martinez-Rossi
Michel Monod
Ekaterina Shelest
Richard C. Barton
Elizabeth Birch
Axel A. Brakhage
Zehua Chen
Sarah J. Gurr
David Heiman
Joseph Heitman
Idit Kosti
Antonio Rossi
Sakina Saif
Marketa Samalova
Charles W. Saunders
Terrance Shea
Richard C. Summerbell
Jun Xu
Sarah Young
Qiandong Zeng
Bruce W. Birren
Christina A. Cuomo
Theodore C. White
Comparative Genome Analysis of <italic toggle="yes">Trichophyton rubrum</italic> and Related Dermatophytes Reveals Candidate Genes Involved in Infection
description 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. IMPORTANCE Athlete’s foot, jock itch, ringworm, and nail infections are common fungal infections, all caused by fungi known as dermatophytes (fungi that infect skin). This report presents the genome sequences of Trichophyton rubrum, the most frequent cause of athlete’s foot, as well as four other common dermatophytes. Dermatophyte genomes are enriched for four gene classes that may contribute to the ability of these fungi to cause disease. These include (i) proteases secreted to degrade skin; (ii) kinases, including pseudokinases, that are involved in signaling necessary for adapting to skin; (iii) secondary metabolites, compounds that act as toxins or signals in the interactions between fungus and host; and (iv) a class of proteins (LysM) that appear to bind and mask cell wall components and carbohydrates, thus avoiding the host’s immune response to the fungi. These genome sequences provide a strong foundation for future work in understanding how dermatophytes cause disease.
format article
author Diego A. Martinez
Brian G. Oliver
Yvonne Gräser
Jonathan M. Goldberg
Wenjun Li
Nilce M. Martinez-Rossi
Michel Monod
Ekaterina Shelest
Richard C. Barton
Elizabeth Birch
Axel A. Brakhage
Zehua Chen
Sarah J. Gurr
David Heiman
Joseph Heitman
Idit Kosti
Antonio Rossi
Sakina Saif
Marketa Samalova
Charles W. Saunders
Terrance Shea
Richard C. Summerbell
Jun Xu
Sarah Young
Qiandong Zeng
Bruce W. Birren
Christina A. Cuomo
Theodore C. White
author_facet Diego A. Martinez
Brian G. Oliver
Yvonne Gräser
Jonathan M. Goldberg
Wenjun Li
Nilce M. Martinez-Rossi
Michel Monod
Ekaterina Shelest
Richard C. Barton
Elizabeth Birch
Axel A. Brakhage
Zehua Chen
Sarah J. Gurr
David Heiman
Joseph Heitman
Idit Kosti
Antonio Rossi
Sakina Saif
Marketa Samalova
Charles W. Saunders
Terrance Shea
Richard C. Summerbell
Jun Xu
Sarah Young
Qiandong Zeng
Bruce W. Birren
Christina A. Cuomo
Theodore C. White
author_sort Diego A. Martinez
title Comparative Genome Analysis of <italic toggle="yes">Trichophyton rubrum</italic> and Related Dermatophytes Reveals Candidate Genes Involved in Infection
title_short Comparative Genome Analysis of <italic toggle="yes">Trichophyton rubrum</italic> and Related Dermatophytes Reveals Candidate Genes Involved in Infection
title_full Comparative Genome Analysis of <italic toggle="yes">Trichophyton rubrum</italic> and Related Dermatophytes Reveals Candidate Genes Involved in Infection
title_fullStr Comparative Genome Analysis of <italic toggle="yes">Trichophyton rubrum</italic> and Related Dermatophytes Reveals Candidate Genes Involved in Infection
title_full_unstemmed Comparative Genome Analysis of <italic toggle="yes">Trichophyton rubrum</italic> and Related Dermatophytes Reveals Candidate Genes Involved in Infection
title_sort comparative genome analysis of <italic toggle="yes">trichophyton rubrum</italic> and related dermatophytes reveals candidate genes involved in infection
publisher American Society for Microbiology
publishDate 2012
url https://doaj.org/article/e9ff1081a0424d49a5ec7400f55e6702
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