Comparative and functional genomics provide insights into the pathogenicity of dermatophytic fungi.
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.
Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Beutenbergstrasse 11a, Jena, 07745, Germany.
Anke
A
Burmester
Ekaterina
E
Shelest
Gernot
G
Glöckner
Christoph
C
Heddergott
Susann
S
Schindler
Peter
P
Staib
Andrew
A
Heidel
Marius
M
Felder
Andreas
A
Petzold
Karol
K
Szafranski
Marc
M
Feuermann
Ivo
I
Pedruzzi
Steffen
S
Priebe
Marco
M
Groth
Robert
R
Winkler
Wenjun
W
Li
Olaf
O
Kniemeyer
Volker
V
Schroeckh
Christian
C
Hertweck
Bernhard
B
Hube
Theodore C
TC
White
Matthias
M
Platzer
Reinhard
R
Guthke
Joseph
J
Heitman
Johannes
J
Wöstemeyer
Peter F
PF
Zipfel
Michel
M
Monod
Axel A
AA
Brakhage
D000818:Animals; D003883:Arthrodermataceae / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D055028:Comparative Genomic Hybridization; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000382:microbiology; D007633:Keratins / Q000378:metabolism; D005810:Multigene Family; D010447:Peptide Hydrolases / Q000235:genetics; D010802:Phylogeny; D059467:Transcriptome
D005656:Fungal Proteins; D007633:Keratins; D010447:Peptide Hydrolases
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