Comparative and functional genomics provide insights into the pathogenicity of dermatophytic fungi

Genome Biology - Tập 12 - Trang 1-16 - 2011
Anke Burmester1,2, Ekaterina Shelest3, Gernot Glöckner4, Christoph Heddergott1,2, Susann Schindler5,6, Peter Staib7, Andrew Heidel4, Marius Felder4,8, Andreas Petzold4, Karol Szafranski4, Marc Feuermann9, Ivo Pedruzzi9, Steffen Priebe3, Marco Groth4, Robert Winkler6,10, Wenjun Li11, Olaf Kniemeyer1, Volker Schroeckh1, Christian Hertweck6,10, Bernhard Hube6,12, Theodore C White13, Matthias Platzer4, Reinhard Guthke3, Joseph Heitman11, Johannes Wöstemeyer2, Peter F Zipfel5,6, Michel Monod14, Axel A Brakhage1,2
1Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), Jena, Germany
2Institute of Microbiology, Friedrich Schiller University (FSU) Jena, Jena, Germany
3Systems Biology/Bioinformatics group, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), Jena, Germany
4Genome Analysis group, Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Jena, Germany
5Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), Jena, Germany
6Friedrich Schiller University (FSU) Jena, Jena, Germany
7Junior Research Group Fundamental Molecular Biology of Pathogenic Fungi, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), Jena, Germany
8Biocomputing group, Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Jena, Germany
9Swiss-Prot group, SIB, Swiss Institute of Bioinformatics, Geneve, Switzerland
10Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), Jena, Germany
11Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, USA
12Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), Jena, Germany
13Seattle Biomedical Research Institute, University of Washington, Seattle, USA
14Department of Dermatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

Tóm tắt

Millions of humans and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which exclusively infect keratinized host structures. To provide broad insights into the molecular basis of the pathogenicity-associated traits, we report the first genome sequences of two closely phylogenetically related dermatophytes, Arthroderma benhamiae and Trichophyton verrucosum, both of which induce highly inflammatory infections in humans. 97% of the 22.5 megabase genome sequences of A. benhamiae and T. verrucosum are unambiguously alignable and collinear. To unravel dermatophyte-specific virulence-associated traits, we compared sets of potentially pathogenicity-associated proteins, such as secreted proteases and enzymes involved in secondary metabolite production, with those of closely related onygenales (Coccidioides species) and the mould Aspergillus fumigatus. The comparisons revealed expansion of several gene families in dermatophytes and disclosed the peculiarities of the dermatophyte secondary metabolite gene sets. Secretion of proteases and other hydrolytic enzymes by A. benhamiae was proven experimentally by a global secretome analysis during keratin degradation. Molecular insights into the interaction of A. benhamiae with human keratinocytes were obtained for the first time by global transcriptome profiling. Given that A. benhamiae is able to undergo mating, a detailed comparison of the genomes further unraveled the genetic basis of sexual reproduction in this species. Our results enlighten the genetic basis of fundamental and putatively virulence-related traits of dermatophytes, advancing future research on these medically important pathogens.

Tài liệu tham khảo

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