This study looked for correlations between molecular identification, clinical manifestation, and morphology for Trichophyton interdigitale and Trichophyton mentagrophytes. For this purpose, a total of 110 isolates were obtained from Czech patients with various clinical manifestations of dermatophytosis. Phenotypic characters were analyzed, and the strains were characterized using multilocus sequence typing. Among the 12 measured/scored phenotypic features, statistically significant differences were found only in growth rates at 37 °C and in the production of spiral hyphae, but none of these features is diagnostic. Correlations were found between T. interdigitale and higher age of patients and between clinical manifestations such as tinea pedis or onychomychosis. The MLST approach showed that internal transcribed spacer (ITS) genotyping of T. mentagrophytes isolates has limited practical benefits because of extensive gene flow between sublineages. Based on our results and previous studies, there are few taxonomic arguments for preserving both species names. The species show a lack of monophyly and unique morphology. On the other hand, some genotypes are associated with predominant clinical manifestations and sources of infections, which keep those names alive. This practice is questionable because the use of both names confuses identification, leading to difficulty in comparing epidemiological studies. The current identification method using ITS genotyping is ambiguous for some isolates and is not user-friendly. Additionally, identification tools such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry fail to distinguish these species. To avoid further confusion and to simplify identification in practice, we recommend using the name T. mentagrophytes for the entire complex. When clear differentiation of populations corresponding to T. interdigitale and Trichophyton indotineae is possible based on molecular data, we recommend optionally using a variety rank: T. mentagrophytes var. interdigitale and T. mentagrophytes var. indotineae.

Species in the T. mentagrophytes complex lack support from usual taxonomic methods and simple identification tools are missing or inaccurate. To avoid recurring confusions, we propose naming the entire complex as T. mentagrophytes and optionally use rank variety to classify the observed variability.

Department of Botany Faculty of Science Charles University Prague Czech Republic

Department of Genetics and Microbiology Faculty of Science Charles University Prague Czech Republic

Laboratory of Environmental Microbiology Institute of Microbiology Czech Academy of Sciences Prague Czech Republic

Laboratory of Fungal Genetics and Metabolism Institute of Microbiology Czech Academy of Sciences Prague Czech Republic

Zobrazit více v PubMed

Summerbell RC. Trichophyton, Microsporum, Epidermophyton, and agents of superficial mycoses. In: Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D, eds. Manual of Clinical Microbiology,10th edn.American Society of Microbiology,2011: 1919–1942.

Havlickova B, Czaika V, Friedrich M.. Epidemiological trends in skin mycoses worldwide. Mycoses. 2008; 51: 2–15. PubMed

Klinger M, Theiler M, Bosshard P.. Epidemiological and clinical aspects of Trichophyton mentagrophytes/Trichophyton interdigitale infections in the Zurich area: a retrospective study using genotyping. J Eur Acad Dermatol Venereol. 2021; 35: 1017–1025. PubMed

Heidemann S, Monod M, Gräser Y.. Signature polymorphisms in the internal transcribed spacer region relevant for the differentiation of zoophilic and anthropophilic strains of Trichophyton interdigitale and other species of T. mentagrophytes sensu lato. Br J Dermatol. 2010; 162: 282–295. PubMed

Gräser Y, Kuijpers AFA, Presber W, De Hoog GS.. Molecular taxonomy of Trichophyton mentagrophytes and T. tonsurans. Med Mycol. 1999; 37: 315–330. PubMed

Chollet A, Cattin V, Fratti M, Mignon B, Monod M.. Which fungus originally was Trichophyton mentagrophytes? Historical review and illustration by a clinical case. Mycopathologia. 2015; 180: 1–5. PubMed

Nenoff P, Herrmann J, Gräser Y.. Trichophyton mentagrophytes sive interdigitale? A dermatophyte in the course of time. J Dtsch Dermatol Ges. 2007; 5: 198–202. PubMed

Sun PL, Hsieh HM, Ju YM, Jee SH.. Molecular characterization of dermatophytes of the Trichophyton mentagrophytes complex found in Taiwan with emphasis on their correlation with clinical observations. British Journal of Dermatology. 2010; 163: 1312–1318. PubMed

Beguin H, Pyck N, Hendrickx M, Planard C, Stubbe D, Detandt M.. The taxonomic status of Trichophyton quinckeanum and T. interdigitale revisited: a multigene phylogenetic approach. Med Mycol. 2012; 50: 871–882. PubMed

de Hoog GS, Dukik K, Monod Met al. . Toward a novel multilocus phylogenetic taxonomy for the dermatophytes. Mycopathologia. 2017; 182: 5–31. PubMed PMC

Hubka V, Peano A, Cmokova A, Guillot J.. Common and emerging dermatophytoses in animals: well-known and new threats. In: Seyedmousavi S, de Hoog GS, Guillot J, Verweij PE, eds. Emerging and Epizootic Fungal Infections in Animals. Springer; 2018: 31–79.

Tang C, Kong X, Ahmed SAet al. . Taxonomy of the Trichophyton mentagrophytes/T. interdigitale species complex harboring the highly virulent, multiresistant genotype T. indotineae. Mycopathologia. 2021; 186: 315–326. PubMed PMC

Schönborn C. Spezielle Pilzdiagnostik in Medizinische Mikrobiologie, Immunologie und Epidemiologie (Band IV/2). 2. neubearbeitete, erweiterte Auflage. Thieme Verlag, 1982.

Reiss E, Shadomy HJ, Lyon GM.. Fundamental Medical Mycology. John Wiley & Sons; 2011.

Campbell CK, Johnson EM, Warnock DW.. Identification of Pathogenic Fungi. 2nd ed.Wiley-Blackwell, 2013: 337.

Uhrlaß S, Verma SB, Gräser Yet al. . Trichophyton indotineae—An emerging pathogen causing recalcitrant dermatophytoses in India and worldwide—a multidimensional perspective. J Fungi. 2022; 8: 757. PubMed PMC

Taghipour S, Pchelin IM, Zarei Mahmoudabadi Aet al. . Trichophyton mentagrophytes and T. interdigitale genotypes are associated with particular geographic areas and clinical manifestations. Mycoses. 2019; 62: 1084–1091. PubMed

Kano R, Kimura U, Kakurai Met al. . Trichophyton indotineae sp. nov.: a new highly terbinafine-resistant anthropophilic dermatophyte species. Mycopathologia. 2020; 185: 947–958. PubMed

Nenoff P, Verma SB, Vasani Ret al. . The current Indian epidemic of superficial dermatophytosis due to Trichophyton mentagrophytes—A molecular study. Mycoses. 2019; 62: 336–356. PubMed

Kumar M, Thomas P, Athira Vet al. . Molecular Epidemiology of Trichophyton infections among canines from Northern India. J Med Mycol. 2023; 33: 101352. PubMed

Jabet A, Brun S, Normand A-Cet al. . Extensive dermatophytosis caused by terbinafine-resistant Trichophyton indotineae, France. Emerg Infect Dis. 2022; 28: 229. PubMed PMC

Dhib I, Khammari I, Yaacoub Aet al. . Relationship between phenotypic and genotypic characteristics of Trichophyton mentagrophytes strains isolated from patients with dermatophytosis. Mycopathologia. 2017; 182: 487–493. PubMed

Suh S-O, Grosso KM, Carrion ME.. Multilocus phylogeny of the Trichophyton mentagrophyte s species complex and the application of matrix-assisted laser desorption/ionization–time-of-flight (MALDI-TOF) mass spectrometry for the rapid identification of dermatophytes. Mycologia. 2018; 110: 118–130. PubMed

Nenoff P, Verma SB, Ebert Aet al. . Spread of terbinafine-resistant Trichophyton mentagrophytes Type VIII (India) in Germany–“The Tip of the Iceberg?”. J Fungi. 2020; 6: 207. PubMed PMC

Hainsworth S, Hubka V, Lawrie AC, Carter D, Vanniasinkam T, Grando D.. Predominance of Trichophyton interdigitale revealed in podiatric nail dust collections in Eastern Australia. Mycopathologia. 2020; 185: 175–185. PubMed

White TJ, Bruns TD, Lee SBet al. . Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics. PCR Protocols: A Guide to Methods and Applications,18,1990:315–322.

Gardes M, Bruns TD.. ITS primers with enhanced specificity for basidiomycetes--application to the identification of mycorrhizae and rusts. Mol Ecol. 1993; 2: 113–118.. doi:10.1111/j.1365-294X.1993.tb00005.x. PubMed DOI

Glass NL, Donaldson GC.. Development of primer sets designed for use with the PCR to amplify conserved genes from filamentous ascomycetes. Appl Environ Microbiol. 1995; 61: 1323–1330. PubMed PMC

Mirhendi H, Makimura K, de Hoog GSet al. . Translation elongation factor 1-alpha gene as a potential taxonomic and identification marker in dermatophytes. Med Mycol. 2015; 53:215–224. PubMed

Hubka V, Nováková A, Jurjević Žet al. . Polyphasic data support the splitting of Aspergillus candidus into two species; proposal of Aspergillus dobrogensis sp. nov. Int J Syst Evol Microbiol. 2018;68:995–1011. PubMed

Katoh K, Rozewicki J, Yamada KD.. MAFFT online service: multiple sequence alignment, interactive sequence choice and visualization. Brief Bioinform. 2019;20:1160–1166. PubMed PMC

Lanfear R, Frandsen PB, Wright AM, Senfeld T, Calcott B. PartitionFinder 2: new methods for selecting partitioned models of evolution for molecular and morphological phylogenetic analyses. Mol Biol Evol. 2017;34:772–773. PubMed

Minh BQ, Schmidt HA, Chernomor Oet al. . IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era. Mol Biol Evol. 2020; 37: 1530–1534. PubMed PMC

Letunic I, Bork P.. Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res. 2021; 49: W293–W296. PubMed PMC

Leigh JW, Bryant D.. POPART: full-feature software for haplotype network construction. Methods Ecol Evol. 2015; 6: 1110–1116.

Clement M, Posada D, Crandall KA.. TCS: a computer program to estimate gene genealogies. Mol Ecol. 2000; 9: 1657–1659. PubMed

Kano R, Kawasaki M, Mochizuki T, Hiruma M, Hasegawa A.. Mating genes of the Trichophyton mentagrophytes complex. Mycopathologia. 2012; 173: 103–112. PubMed

Čmoková A, Rezaei-Matehkolaei A, Kuklová Iet al. . Discovery of new Trichophyton members, T. persicum and T. spiraliforme spp. nov., as a cause of highly inflammatory tinea cases in Iran and Czechia. Microbiol Spectr. 2021; 9: e00284–21. PubMed PMC

Kornerup A, Wanscher JH.. Methuen Handbook of Colour.Methuen & Co. Ltd,1967.

R Core Team . R: A Language and Environment for Statistical Computing. Vienna: R Foundation for Statistical Computing,2021.

Pinheiro JC, Bates DM, DebRoy SS, Sarkar D. nlme: linear and nonlinear mixed effects models. R package version 3. 2013; 1–150.. http://CRAN.R-project.org/package=nlme.

Shaw D, Singh S, Dogra Set al. . MIC and upper limit of wild-type distribution for 13 antifungal agents against a Trichophyton mentagrophytes-Trichophyton interdigitale complex of Indian origin. Antimicrob Agents Chemother. 2020; 64: e01964–19. PubMed PMC

Symoens F, Jousson O, Planard Cet al. . Molecular analysis and mating behaviour of the Trichophyton mentagrophytes species complex. Int J Med Microbiol. 2011; 301: 260–266. PubMed

Bontems O, Fratti M, Salamin K, Guenova E, Monod M.. Epidemiology of dermatophytoses in Switzerland according to a survey of dermatophytes isolated in Lausanne between 2001 and 2018. J Fungi. 2020; 6: 95. PubMed PMC

Frías-De-León MG, Martínez-Herrera E, Atoche-Diéguez CEet al. . Molecular identification of isolates of the Trichophyton mentagrophytes complex. Int J Med Sci. 2020; 17: 45–52. PubMed PMC

Gräser Y, De Hoog S, Summerbell R.. Dermatophytes: recognizing species of clonal fungi. Med Mycol. 2006; 44: 199–209. PubMed

Nenoff P, Verma SB, Uhrlaß S, Burmester A, Gräser Y.. A clarion call for preventing taxonomical errors of dermatophytes using the example of the novel Trichophyton mentagrophytes genotype VIII uniformly isolated in the Indian epidemic of superficial dermatophytosis. Mycoses. 2019; 62: 6–10. PubMed

Kong X, Tang C, Singh Aet al. . Antifungal susceptibility and mutations in the squalene epoxidase gene in dermatophytes of the Trichophyton mentagrophytes species complex. Antimicrob Agents Chemother. 2021; 65: e00056–21. PubMed PMC

Kandemir H, Dukik K, Hagen F, Ilkit M, Gräser Y, de Hoog GS.. Polyphasic discrimination of Trichophyton tonsurans and T. equinum from humans and horses. Mycopathologia. 2020; 185: 113–122. PubMed

Čmoková A, Kolařík M, Guillot Jet al. . Host-driven subspeciation in the hedgehog fungus, Trichophyton erinacei, an emerging cause of human dermatophytosis. Persoonia. 2022; 48:203–218. PubMed PMC

Čmoková A, Kolařík M, Dobiáš Ret al. . Resolving the taxonomy of emerging zoonotic pathogens in the Trichophyton benhamiae complex. Fungal Divers. 2020; 104: 333–387.

De Queiroz K. Nodes, branches, and phylogenetic definitions. Syst Biol. 2013; 62: 625–632. PubMed

Kapli P, Yang Z, Telford MJ.. Phylogenetic tree building in the genomic age. Nat Rev Genet. 2020; 21: 428–444. PubMed

Metin B, Heitman J.. She loves me, she loves me not: on the dualistic asexual/sexual nature of dermatophyte fungi. Mycopathologia. 2020; 185: 87–101. PubMed PMC

Bian C, Kusaya Y, Sklenář Fet al. . Reducing the number of accepted species in Aspergillus series Nigri. Stud Mycol. 2022; 102: 95–132. PubMed PMC

Sklenář F, Glässnerová K, Jurjević Žet al. . Taxonomy of Aspergillus series Versicolores: species reduction and lessons learned about intraspecific variability. Stud Mycol. 2022; 102: 53–93. PubMed PMC

Gupta AK, Jain HC, Lynde CW, Macdonald P, Cooper EA, Summerbell RC. Prevalence and epidemiology of onychomycosis in patients visiting physicians' offices: a multicenter canadian survey of 15,000 patients. J Am Acad Dermatol. 2000; 43:244–248. PubMed

Frealle E, Rodrigue M, Gantois Net al. . Phylogenetic analysis of Trichophyton mentagrophytes human and animal isolates based on MnSOD and ITS sequence comparison. Microbiology. 2007; 153: 3466–3477. PubMed

Pchelin IM, Azarov DV, Churina MAet al. . Species boundaries in the Trichophyton mentagrophytes/T. interdigitale species complex. Med Mycol. 2019; 57: 781–789. PubMed

Arendrup MC, Kahlmeter G, Guinea J, Meletiadis J. Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST) . How to: perform antifungal susceptibility testing of microconidia-forming dermatophytes following the new reference EUCAST method E. Def 11.0, exemplified by Trichophyton. Clin Microbiol Infect. 2021; 27:55–60. PubMed

Tang C, Ahmed S, Deng Set al. . Detection of emerging genotypes in Trichophyton mentagrophyt es species complex: a proposal for handling biodiversity in dermatophytes. Front Microbiol. 2022; 13: 960190. PubMed PMC

Normand A-C, Moreno-Sabater A, Jabet Aet al. . MALDI-TOF mass spectrometry online identification of Trichophyton indotineae using the MSI-2 application. J Fungi. 2022; 8: 1103. PubMed PMC

Moreno-Sabater A, Normand A-C, Bidaud A-Let al. . Terbinafine resistance in dermatophytes: a French multicenter prospective study. J Fungi. 2022; 8: 220. PubMed PMC

Pchelin IM, Zlatogursky VV, Rudneva MVet al. . Reconstruction of phylogenetic relationships in dermatomycete genus Trichophyton Malmsten 1848 based on ribosomal internal transcribed spacer region, partial 28S rRNA and beta-tubulin genes sequences. Mycoses. 2016; 59: 566–575. PubMed

Singh A, Masih A, Monroy-Nieto Jet al. . A unique multidrug-resistant clonal Trichophyton population distinct from Trichophyton mentagrophytes/Trichophyton interdigitale complex causing an ongoing alarming dermatophytosis outbreak in India: Genomic insights and resistance profile. Fungal Genet Biol. 2019; 133: 103266. PubMed

Resolving Phylogenetic Relationships Within the Trichophyton mentagrophytes Complex: A RADseq Genomic Approach Challenges Status of 'Terbinafine-Resistant' Trichophyton indotineae as Distinct Species

Trichophyton mentagrophytes ITS genotype VII infections among men who have sex with men in France: An ongoing phenomenon

First Step on the Way to Identify Dermatophytes Using Odour Fingerprints