Mycopathologia DOI 10.1007/s11046-016-0073-9 Toward a Novel Multilocus Phylogenetic Taxonomy for the Dermatophytes G. Sybren de Hoog . Karolina Dukik . Michel Monod . Ann Packeu . Dirk Stubbe . Marijke Hendrickx . Christiane Kupsch . J. Benjamin Stielow . Joanna Freeke . Markus Go¨ker . Ali Rezaei-Matehkolaei . Hossein Mirhendi . Yvonne Gra¨ser Received: 1 July 2016 / Accepted: 28 September 2016 Ó The Author(s) 2016. This article is published with open access at Springerlink.com Abstract Type and reference strains of members of anthropophilic dermatophytes in Trichophyton and the onygenalean family Arthrodermataceae have been Epidermophyton, along with some zoophilic species sequenced for rDNA ITS and partial LSU, the riboso- that regularly infect humans. Microsporum is restricted mal 60S protein, and fragments of b-tubulin and to some species around M. canis, while the geophilic translation elongation factor 3. The resulting phyloge- species and zoophilic species that are more remote netic trees showed a large degree of correspondence, from the human sphere are divided over Arthroderma, and topologies matched those of earlier published Lophophyton and Nannizzia. A new genus Guar- phylogenies demonstrating that the phylogenetic rep- romyces is proposed for Keratinomyces ceretanicus. resentation of dermatophytes and dermatophyte-like Thirteen new combinations are proposed; in an over- fungi has reached an acceptable level of stability. All view of all described species it is noted that the largest trees showed Trichophyton to be polyphyletic. In the number of novelties was introduced during the decades present paper, Trichophyton is restricted to mainly the 1920–1940, when morphological characters were used derived clade, resulting in classification of nearly all in addition to clinical features. Species are neo- or epi- typified where necessary, which was the case in Arthroderma curreyi, Epidermophyton floccosum, Electronic supplementary material The online version of Lophophyton gallinae, Trichophyton equinum, T. this article (doi:10.1007/s11046-016-0073-9) contains supple- mentagrophytes, T. quinckeanum, T. schoenleinii, T. mentary material, which is available to authorized users. G. S. de Hoog (&) Á K. Dukik Á J. B. Stielow Á J. Freeke G. S. de Hoog CBS-KNAW Fungal Biodiversity Centre, Utrecht, Shanghai Institute of Medical Mycology, Changzheng The Netherlands Hospital, Second Military Medical University, Shanghai, e-mail: [email protected] China G. S. de Hoog Á K. Dukik G. S. de Hoog Institute of Biodiversity and Ecosystem Dynamics, Biological Sciences Department, Faculty of Science, University of Amsterdam, Amsterdam, The Netherlands King Abdulaziz University, Jeddah, Saudi Arabia G. S. de Hoog M. Monod Basic Pathology Department, Federal University of Department of Dermatology, Centre Hospitalier Parana´ State, Curitiba, Parana´, Brazil Universitaire Vaudois, Lausanne, Switzerland G. S. de Hoog Peking University Health Science Center, Research Center for Medical Mycology, Beijing, China 123 Mycopathologia soudanense, and T. verrucosum. In the newly proposed enormously. Species were defined on the basis of taxonomy, Trichophyton contains 16 species, Epider- combined clinical pictures and morphological charac- mophyton one species, Nannizzia 9 species, Microspo- ters in vitro. Sixteen human-associated species were rum 3 species, Lophophyton 1 species, Arthroderma 21 introduced between 1870 and 1920, with Sabouraud’s species and Ctenomyces 1 species, but more detailed [5] magistral overview of the dermatophytes setting a studies remain needed to establish species borderlines. new standard. During the decades that followed, Each species now has a single valid name. Two new application of the new methodological standard led genera are introduced: Guarromyces and Paraphyton. to an explosion of new species and recombined names The number of genera has increased, but species that (Fig. 1). Generic concepts remained confused, leading are relevant to routine diagnostics now belong to to repeated name changes with a total of 350 names smaller groups, which enhances their identification. around the year 1950. Subsequently anamorph nomen- clature stabilized by the wide acceptance of Epider- Keywords Arthrodermataceae Á Dermatophytes Á mophyton, Microsporum and Trichophyton as the Phylogeny Á Taxonomy Á Trichophyton genera covering all dermatophytes. Culture and microscopic morphology worked well as diagnostic parameters when fresh isolates were used, but were difficult to maintain and reproduce Introduction because of rapid degeneration. Standardization with reference strains was therefore difficult, and this led to The dermatophytes belong to the oldest groups of the introduction of numerous taxa that are now microorganisms that have been recognized as agents regarded as synonyms of earlier described species. In of human disease. The taxonomy of these fungi was addition, diverse types of morphological mutants were initiated in 1841 with the studies of Robert Remak and described as separate taxa, such as Keratinomyces David Gruby [1]. Between 1840 and 1875, five of the longifusus, which turned out to be Microsporum main species known today, viz. Microsporum audoui- fulvum with strongly coherent conidia [6]. This nii, Epidermophyton floccosum, Trichophyton schoen- misclassification is an unavoidable consequence of a leinii, T. tonsurans and T. mentagrophytes had already diagnostic system based on the phenotype. Similar been described; this was several decades before the misjudgments of mutants of a single species also discovery of Pasteur’s invention of axenic culture [2]. occurred elsewhere, sometimes unknowingly leading The only ubiquitous modern dermatophyte missing to the description of a separate genus for the mutant: from the list is Trichophyton rubrum [3], which has compare, e.g., the genus pairs Bipolaris/Dissitimurus, been hypothesized to have emerged in the twentieth Scedosporium/Polycytella, Exophiala/Sarcinomyces, century [4]. or Trichosporon/Fissuricella [7]. In addition, several After Pasteur’s time, culturing of dermatophytes dermatophytes are known which do not or poorly and description of new species has taken off sporulate in culture and thus show very limited A. Packeu Á D. Stubbe Á M. Hendrickx A. Rezaei-Matehkolaei Mycology and Aerobiology, Scientific Institute of Public Health Research Institute, Infectious and Tropical Health, Brussels, Belgium Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran C. Kupsch Á Y. Gra¨ser (&) Institute of Microbiology and Hygiene, University A. Rezaei-Matehkolaei Medicine Berlin - Charite´, Berlin, Germany Department of Medical Mycology, School of Medicine, e-mail: [email protected] Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran J. B. Stielow Á J. Freeke Thermo Fisher Scientific, Landsmeer, The Netherlands H. Mirhendi Department of Medical Parasitology and Mycology, M. Go¨ker School of Public Health, Tehran University of Medical Leibniz Institute DSMZ-German Collection of Sciences, Tehran, Iran Microorganisms and Cell Cultures, Brunswick, Germany 123 Mycopathologia clinical clinical + culture mang molecular anthropophiles anthropophiles 100 95 242 90 80 76 70 60 50 42 103 40 35 33 30 27 27 23 24 21 20 15 11 rubrum T. 9 9 8 7 7 8 7 48 10 5 3 3 4 3 4 2 1 2 1 2 1 1 2 24 10 0 1891-1895 1911-1915 1916-1920 1936-1940 1941-1945 1946-1950 1961-1965 1966-1970 1971-1975 1981-1985 1986-1990 1991-1995 2006-2010 2011-2015 1840-1845 1846-1850 1856-1860 1861-1865 1866-1870 1871-1875 1876-1880 1881-1885 1886-1890 1896-1900 1901-1905 1906-1910 1921-1925 1931-1935 1951-1955 1956-1960 1976-1980 1996-2000 2001-2005 1851-1855 1926-1930 Fig. 1 Number of name changes of members of Arthroder- bar at the right shows the approximate number of existing mataceae during the period 1840–2015, with 5-year increments. anthropophilic species (n = 10), the number of times these have The largest number of new names was created when morphol- been described (basionyms: n = 103) and the total number of ogy was added to clinical data as criteria for species distinction. name changes for these 10 species (n = 242). Possible [7] and The period 1960–1995 is marked by the addition of teleomorph proven synonyms of Trichophyton rubrum are listed in ocher names, leading to dual nomenclature of the dermatophytes. The (n = 48), of which (n = 24) were basionyms, in red phenotypic characteristics. Classically such species well as related non-pathogenic species like Trichophy- were partly based on clinical symptoms, e.g., T. ton terrestre and T. ajelloi, were found to produce concentricum or T. schoenleinii, but many more, sexual states, for which the genera Arthroderma and undescribed species may exist [8]. Nannizzia were introduced. This led to a new boom in In the last decades of the twentieth century, it the number of names (Fig. 1) and marked the intro- became obvious that morphology had its limitations duction of dual nomenclature for dermatophytes. The and could not be used as sole characteristic for delineation of sexual interaction began to take an classification or identification. Given these problems, unusual course when Stockdale [12] discovered that Weitzman et al. [9] introduced an additional character members of many apparently non-mating species set in the form of physiological parameters, so-called could be induced to reveal their mating type in an trichophyton-agars utilizing the ability of strains to incomplete mating reaction with testers of Arthro- assimilate