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

Abstract

BackgroundMillions 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.Results97% 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.ConclusionsOur results enlighten the genetic basis of fundamental and putatively virulence-related traits of dermatophytes, advancing future research on these medically important pathogens.

The Arthroderma benhamiae Hydrophobin HypA Mediates Hydrophobicity and Influences Recognition by Human Immune Effector Cells

“…They are usually transmitted from the natural animal host, the guinea pig (13,16). Recently, we reported the complete genome sequence of A. benhamiae (10). Because, in addition, A. benhamiae is amenable to genetic manipulation and grows well under laboratory conditions, this dermatophyte represents an excellent model organism for the elucidation of pathogenicity-associated traits.…”

Development of an Enzyme-Linked Immunosorbent Assay for Serodiagnosis of Ringworm Infection in Cattle

“…Although several secreted proteases from dermatophytes have been obtained as recombinant proteins, no T. verrucosum-secreted proteases are currently available in recombinant form. In spite of their different ecologies, the genome of T. rubrum (21) proved to be most closely related to the genomes of T. verrucosum and Arthroderma benhamiae, two phylogenetically closely related dermatophytes that induce highly inflammatory cutaneous infections in humans (22,23). In addition, most Trichophyton species revealed similar secreted protein profiles (24).…”

Fungi on the Skin: Dermatophytes and Malassezia

“…These were completed and published in 2011 and 2012 (Burmester et al 2011;Martinez et al 2012). The species that were sequenced include T. rubrum, T. tonsurans, T. equinum, M. canis, M. gypseum, A. benhamiae, and T. verrucosum.…”