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

被引:151
作者
Burmester, Anke [1 ,2 ]
Shelest, Ekaterina [3 ]
Gloeckner, Gernot [4 ]
Heddergott, Christoph [1 ,2 ]
Schindler, Susann [5 ]
Staib, Peter [6 ]
Heidel, Andrew [4 ]
Felder, Marius [4 ,7 ]
Petzold, Andreas [4 ]
Szafranski, Karol [4 ]
Feuermann, Marc [8 ]
Pedruzzi, Ivo [8 ]
Priebe, Steffen [3 ]
Groth, Marco [4 ]
Winkler, Robert [9 ]
Li, Wenjun [10 ]
Kniemeyer, Olaf [1 ]
Schroeckh, Volker [1 ]
Hertweck, Christian [9 ]
Hube, Bernhard [11 ]
White, Theodore C. [12 ]
Platzer, Matthias [4 ]
Guthke, Reinhard [3 ]
Heitman, Joseph [10 ]
Woestemeyer, Johannes [2 ]
Zipfel, Peter F. [5 ]
Monod, Michel [13 ]
Brakhage, Axel A. [1 ,2 ]
机构
[1] Hans Knoll Inst HKI, Dept Mol & Appl Microbiol, Leibniz Inst Nat Prod Res & Infect Biol, D-07745 Jena, Germany
[2] Univ Jena, Inst Microbiol, D-07743 Jena, Germany
[3] Hans Knoll Inst HKI, Syst Biol Bioinformat Grp, Leibniz Inst Nat Prod Res & Infect Biol, D-07745 Jena, Germany
[4] Fritz Lipmann Inst FLI, Genome Anal Grp, Leibniz Inst Age Res, D-07745 Jena, Germany
[5] Hans Knoll Inst HKI, Dept Infect Biol, Leibniz Inst Nat Prod Res & Infect Biol, D-07745 Jena, Germany
[6] Hans Knoll Inst HKI, Jr Res Grp Fundamental Mol Biol Pathogen Fungi, Leibniz Inst Nat Prod Res & Infect Biol, D-07745 Jena, Germany
[7] Fritz Lipmann Inst FLI, Biocomp Grp, Leibniz Inst Age Res, D-07745 Jena, Germany
[8] Swiss Inst Bioinformat, Swiss Prot Grp, SIB, CH-1204 Geneva, Switzerland
[9] Hans Knoll Inst HKI, Dept Biomol Chem, Leibniz Inst Nat Prod Res & Infect Biol, D-07745 Jena, Germany
[10] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA
[11] Hans Knoll Inst HKI, Dept Microbial Pathogen Mech, Leibniz Inst Nat Prod Res & Infect Biol, D-07745 Jena, Germany
[12] Univ Washington, Seattle Biomed Res Inst, Seattle, WA 98109 USA
[13] CHU Vaudois, Dept Dermatol, CH-1011 Lausanne, Switzerland
来源
GENOME BIOLOGY | 2011年 / 12卷 / 01期
基金
美国国家卫生研究院;
关键词
DIFFERENTIAL EXPRESSION ANALYSIS; INTERNAL TRANSCRIBED SPACER-1; TRICHOPHYTON-RUBRUM; ARTHRODERMA-BENHAMIAE; GENE-EXPRESSION; IN-VITRO; IDENTIFICATION; TERBINAFINE; PHYLOGENIES; SEQUENCES;
D O I
10.1186/gb-2011-12-1-r7
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: 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. Results: 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. Conclusions: Our results enlighten the genetic basis of fundamental and putatively virulence-related traits of dermatophytes, advancing future research on these medically important pathogens.
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页数:16
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