Generating and Testing Molecular Hypotheses in the Dermatophytes

Dermatophytes are the most common cause of fungal infec- tions worldwide, impacting millions of individuals annually. In the United States alone, this translates into an economic im- pact on the health care system estimated to exceed $400 mil- lion a year for treatment alone (8, 46). A recent survey con- ducted in 16 European countries has shown that more than one-third (35 to 40%) of the 90,000 participants were suffering with a fungal foot disease, mainly caused by dermatophytes (4). In a recent study, 22 to 50% of children in a U.S. day care center exhibited symptoms of dermatophytic scalp infections (2). Despite the prominence of dermatophyte infections and their resulting socioeconomic consequences, the research and medical communities lack a sophisticated understanding of these organisms' biology. Consequently, effective preventatives and therapeutics are lacking. These deficiencies are in large part due to the lack of genetic tools available for the study of these fungi and their host specificities. Several research efforts are now poised to produce genomic and molecular resources that will enable the molecular characterization of dermato- phytes. These resources will soon be available for use by the larger research community to address many questions about the biology and pathogenesis of dermatophytes. This review will elaborate on the current status of these resources and their importance to the study of the dermatophytes. sides of the foot. The destruction of the skin barrier can result in bacterial superinfection. Nail infections are associated with thickening, discoloration, and pain. Scalp infections can cause irreversible hair loss. Organisms. All of the dermatophytes are ascomycetous molds, members of the class Euascomycetes that also includes Aspergillus species and the dimorphic fungi (Fig. 1) (34). The dermatophytes are classified into three genera: Trichophyton, Microsporum, and Epidermophton. As can be seen in Fig. 2, the dermatophytes are a monophyletic clade, although the as- signed genus designations within the clade do not strictly seg- regate (24). At least 31 of the dermatophyte species are known to be human pathogens, although additional unidentified spe- cies (including pathogens) are likely to exist. Species of dermatophytes are characterized based on their environmental niche: geophilic (soil dwelling), zoophilic (ani- mals), and anthropophilic (human specific). The geophilic spe- cies (Fig. 2, highlighted in green) are commonly found in soil and only rarely are found in human infections. The zoophilic species (Fig. 2, highlighted in red) colonize animals and can be transmitted occasionally to humans. These species are respon- sible for about 30% of human dermatophytoses and usually cause acute inflammation upon infection. The anthropophilic species (Fig. 2, highlighted in black) have adjusted to growth in humans and do not appear to have an animal reservoir. They are responsible for the majority (ca. 70%) of human dermato- phytoses. These species cause chronic, slowly progressing dis- ease, suggesting that the fungi have adapted to human hosts. Genome sequences from each of these types are currently being prepared and will enable a comparative genomic ap- proach to host specificity.