, 166:319 | Cite as

Strain Differentiation of Dermatophytes

  • Susan M. Abdel-Rahman


As molecular-based investigations begin to uncover the large degree of genetic variation that can exist within dermatophyte species, and population-based studies reveal exceedingly high rates of endemicity for these organisms, species typing has become inadequate to gain insight into these pathogens and the nature of the infections that they cause. This review examines studies that have applied strain typing strategies to explore intra-specific genetic diversity among the dermatophytes in attempts to address a number of relevant clinico-epidemiologic questions about these common fungal pathogens.


Trichophyton Microsporum Tinea Epidemiology Evolution Population studies 



Randomly amplified polymorphic DNA


Arbitrarily primed polymerase chain reaction


Randomly amplified monomorphic DNA


Single-stranded conformational polymorphism


Amplified fragment length polymorphism


Restriction fragment length polymorphism


Variable number tandem repeats


Internal transcribed spacer


Non-transcribed spacer


  1. 1.
    Soll DR. The ins and outs of DNA fingerprinting the infectious fungi. Clin Microbiol Rev. 2000;13:332–70.PubMedCrossRefGoogle Scholar
  2. 2.
    Taylor JW, Geiser DM, Burt A, Koufopanou V. The evolutionary biology and population genetics underlying fungal strain typing. Clin Microbiol Rev. 1999;12:126–46.PubMedGoogle Scholar
  3. 3.
    Hunter PR. A critical review of typing methods for Candida albicans and their applications. Crit Rev Microbiol. 1991;17:417–34.PubMedCrossRefGoogle Scholar
  4. 4.
    Olive DM, Bean P. Principles and applications of methods for DNA-based typing of microbial organisms. J Clin Microbiol. 1999;37:1661–9.PubMedGoogle Scholar
  5. 5.
    Gil-Lamaignere C, Roilides E, Hacker J, Muller FMC. Molecular typing for fungi-a critical review of the possibilities and limitations of currently and future methods. Clin Microbiol Infect. 2003;9:172–85.PubMedCrossRefGoogle Scholar
  6. 6.
    Liu D, Coloe S, Pedersen J, Baird R. Use of arbitrarily primed polymerase chain reaction to differentiate Trichophyton dermatophytes. FEMS Microbiol Lett. 1996;136:147–50.PubMedCrossRefGoogle Scholar
  7. 7.
    Zhong Z, Li R, Li D, Wang D. Typing of common dermatophytes by random amplification of polymorphic DNA. Jpn J Med Mycol. 1997;38:239–46.Google Scholar
  8. 8.
    Kim JA, Takizawa K, Fukushima K, Nishimura K, Miyaji M. Identification and genetic homogeneity of Trichophyton tonsurans isolated from several regions by random amplified polymorphic DNA. Mycopathologia 1999;145:1–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Gräser Y, Kühnisch J, Presber W. Molecular markers reveal exclusively clonal reproduction in Trichophyton rubrum. J Clin Microbiol. 1999;37:3713–7.PubMedGoogle Scholar
  10. 10.
    Howell SA, Barnard RJ, Humphreys F. Application of molecular typing methods to dermatophyte species that cause skin and nail infections. J Med Microbiol. 1999;48:33–40.PubMedGoogle Scholar
  11. 11.
    Faggi E, Pini G, Campisi E, Bertellini C, Difonzo E, Mancianti F. Application of PCR to distinguish common species of dermatophytes. J Clin Microbiol. 2001;39:3382–5.PubMedCrossRefGoogle Scholar
  12. 12.
    Kac G, Bougnoux ME, Feuilhade de Chauvin M, Sene S, Derouin F. Genetic diversity among T. mentagrophytes isolates using random amplified polymorphic DNA method. Br J Dermatol. 1999;140:839–44.PubMedCrossRefGoogle Scholar
  13. 13.
    Baeza LC, Mendes-Giannini MJS. Strain differentiation of Trichophyton rubrum by random amplification of polymorphic DNA (RAPD). Rev Inst Med Trop Sao Paulo. 2004;46:339–41.PubMedGoogle Scholar
  14. 14.
    Baeza LC, Matsumoto MT, Almeida AMF, Mendes-Giannini MJS. Strain differentiation of Trichophyton rubrum by randomly amplified polymorphic DNA and analysis of rDNA nontranscribed spacer. J Med Microbiol. 2006;55:429–36.PubMedCrossRefGoogle Scholar
  15. 15.
    Sampaio P, Gusmão L, Correia A, Alves C, Rodrigues AG, Pina-Vaz C, Amorim A, Pais C. New microsatellite multiplex PCR for Candida albicans strain typing reveals microevolutionary changes. J Clin Microbiol. 2005;43:3869–76.PubMedCrossRefGoogle Scholar
  16. 16.
    Ohst T, de Hoog S, Presber W, Stavrakieva V, Gräser Y. Origins of microsatellite diversity in the Trichophyton rubrum-T. violaceum clade (Dermatophytes). J Clin Microbiol. 2004;42:4444–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Gräser Y, Frohlich J, Presber W, de Hoog S. Microsatellite markers reveal geographic population differentiation in Trichophyton rubrum. J Med Microbiol. 2007;56:1058–65.PubMedCrossRefGoogle Scholar
  18. 18.
    Kaszubiak A, Klein S, de Hoog GS, Gräser Y. Population structure and evolutionary origins of Microsporum canis, M. ferrugineum and M. audouinii. Infect Genet Evol. 2004;4:179–86.PubMedCrossRefGoogle Scholar
  19. 19.
    Cano J, Rezusta A, Sole M, Gil J, Rubio MC, Revillo MJ, Guarro J. Inter-single-sequence-repeat-PCR typing as a new tool for identification of Microsporum canis strains. J Dermatol Sci. 2005;39:17–21.PubMedCrossRefGoogle Scholar
  20. 20.
    Tyler KD, Wang G, Tyler SD, Johnson WM. Factors affecting reliability and reproducibility of amplification-based DNA fingerprinting of representative bacterial pathogens. J Clin Microbiol. 1997;35:339–46.PubMedGoogle Scholar
  21. 21.
    van Belkum A, Kluytmans J, van Leeuwen W, et al. Multicenter evaluation of arbitrarily primed PCR for typing of Staphylococcus aureus strains. J Clin Microbiol. 1995;33:1537–47.PubMedGoogle Scholar
  22. 22.
    Shemer R, Weissman Z, Hashman N, Kornitzer D. A highly polymorphic degenerate microsatellite for molecular strain typing of Candida krusei. Microbiology. 2001;147:2021–8.PubMedGoogle Scholar
  23. 23.
    Metzgar D, van Belkum A, Field D, Haubrich R, Wills C. Random amplification of polymorphic DNA and microsatellite genotyping of pre- and posttreatment isolates of Candida spp. from human immunodeficiency virus-infected patients on different fluconazole regimens. J Clin Microbiol. 1998;36:2308–13.PubMedGoogle Scholar
  24. 24.
    Makimura K, Mochizuki T, Hasegawa A, Uchida K, Saito H, Yamaguchi H. Phylogenetic classification of Trichophyton mentagrophytes complex strains based on DNA sequences of nuclear ribosomal internal transcribed spacer 1 regions. J Clin Microbiol. 1998;36:2629–33.PubMedGoogle Scholar
  25. 25.
    Mochizuki T, Kawasaki M, Ishizaki H, Kano R, Hasegawa A, Tosaki H, Fujihiro M. Molecular epidemiology of Arthroderma benhamiae, an emerging pathogen of dermatophytoses in Japan, by polymorphisms of the non-transcribed spacer region of the ribosomal DNA. J Dermatol Sci. 2001;27:14–20.PubMedCrossRefGoogle Scholar
  26. 26.
    Shin J, Sung J, Park S, Kim J, Lee J, Lee D, Lee E, Yang J. Species identification and strain differentiation of dermatophyte fungi using polymerase chain reaction amplification and restriction enzyme analysis. J Am Acad Dermatol. 2003;48:857–65.PubMedCrossRefGoogle Scholar
  27. 27.
    Gaedigk A, Gaedigk R, Abdel-Rahman SM. Genetic heterogeneity in the rRNA gene locus of Trichophyton tonsurans. J Clin Microbiol. 2003;41:5478–87.PubMedCrossRefGoogle Scholar
  28. 28.
    Yu J, Wan Z, Chen W, Wang W, Li R. Molecular typing study of the Microsporum canis strains isolated from an outbreak of tinea capitis in a school. Mycopathologia. 2004;157:37–41.PubMedCrossRefGoogle Scholar
  29. 29.
    Abliz P, Takizawa K, Nishimura K, Fukushima K, de Souza Motta CM, Magallaos OM, Deng S, Xi L, Vidotto V. Molecular typing of Trichophyton tonsurans by PCR-RFLP of the ribosomal DNA transcriber spacer region. J Dermatol Sci. 2004;36:125–7.PubMedGoogle Scholar
  30. 30.
    Gräser Y, El Fari M, Vilgalys R, Kuijpers AF, de Hoog GS, Presber W, Tietz H. Phylogeny and taxonomy of the family Arthrodermataceae (dermatophytes) using sequence analysis of the ribosomal ITS region. Med Mycol. 1999;37:105–14.PubMedCrossRefGoogle Scholar
  31. 31.
    Mochizuki T, Tanabe H, Kawasaki M, Ishizaki H, Jackson CJ. Rapid identification of Trichophyton tonsurans by PCR-RFLP analysis of ribosomal DNA regions. J Dermatol Sci. 2003;32:25–32.PubMedCrossRefGoogle Scholar
  32. 32.
    Harmsen D, Schwinn A, Brocker EB, Frosch M. Molecular differentiation of dermatophyte fungi. Mycoses. 1999;42:67–70.PubMedCrossRefGoogle Scholar
  33. 33.
    Makimura K, Tamura Y, Mochizuki T, Hasegawa A, Tajiri Y, Hanazawa R, Uchida K, Saito H, Yamaguchi H. Phylogenetic classification and species identification of dermatophyte strains based on DNA sequences of nuclear ribosomal internal transcribed spacer 1 regions. J Clin Microbiol. 1999;37:920–4.PubMedGoogle Scholar
  34. 34.
    Summerbell RC, Haugland RA, Li A, Gupta AK. rRNA gene internal transcribed spacer 1 and 2 sequences of asexual, anthropophilic dermatophytes related to Trichophyton rubrum. J Clin Microbiol. 1999;37:4005–11.PubMedGoogle Scholar
  35. 35.
    Carlotti A, Srikantha T, Schröppel K, Kvaal C, Villard J, Soll DR. A novel repeat sequence (CKRS-1) containing a tandemly repeated sub-element (kre) accounts for differences between Candida krusei strains fingerprinted with the probe CkF1,2. Curr Genet. 1997;31:255–63.PubMedCrossRefGoogle Scholar
  36. 36.
    Jackson CJ, Barton RC, Evans EGV. Species identification and strain differentiation of dermatophyte fungi by analysis of ribosomal-DNA intergenic spacer regions. J Clin Microbiol. 1999;37:931–6.PubMedGoogle Scholar
  37. 37.
    Jackson CJ, Barton RC, Kelly SL, Evans EGV. Strain identification of Trichophyton rubrum by specific amplification of subrepeat elements in the ribosomal DNA nontranscribed spacer. J Clin Microbiol. 2000;38:4527–34.PubMedGoogle Scholar
  38. 38.
    Kamiya A, Kikuchi A, Tomita Y, Kanbe T. PCR and PCR-RFLP techniques targeting the DNA topoisomerase II gene for rapid clinical diagnosis of the etiologic agent of dermatophytosis. J Dermatol Sci. 2004;34:35–48.PubMedCrossRefGoogle Scholar
  39. 39.
    Yazdanparast A, Jackson CJ, Barton RC, Evans EGV. Molecular strain typing of Trichophyton rubrum indicates multiple strain involvement in onychomycosis. Br J Dermatol. 2003;148:51–4.PubMedCrossRefGoogle Scholar
  40. 40.
    Rad MM, Jackson C, Barton RC, Evans EGV. Single strains of Trichophyton rubrum in cases of tinea pedis. J Med Microbiol. 2005;54:725–6.PubMedCrossRefGoogle Scholar
  41. 41.
    de Assis Santos D, de Carvalho Araujo RA, Kohler LM, Machado-Pinto J, Hamdan JS, Cisalpino PS. Molecular typing and antifungal susceptibility of Trichophyton rubrum isolates from patients with onychomycosis pre- and post-treatment. Int J Antimicrob Agents. 2007;29:563–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Gupta AK, Kohli Y, Summerbell RC. Variation in restriction fragment length polymorphisms among serial isolates from patients with Trichophyton rubrum infection. J Clin Microbiol. 2001;39:3260–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Abdel-Rahman SM, Simon S, Wright KJ, Ndjountche L, Gaedigk A. Tracking Trichophyton tonsurans through a large urban childcare center: defining infection prevalence and transmission patterns by molecular stain typing. Pediatrics. 2006;118:2365–73.PubMedCrossRefGoogle Scholar
  44. 44.
    Sugita T, Shiraki Y, Hiruma M. Genotype analysis of the variable internal repeat region in the rRNA gene of Trichophyton tonsurans isolated from Japanese judo practitioners. Microbiol Immunol. 2006;50:57–60.PubMedGoogle Scholar
  45. 45.
    Jackson CJ, Mochizuki T, Barton RC. PCR fingerprinting of Trichophyton mentagrophytes var. interdigitale using polymorphic subrepeat loci in the rDNA nontranscribed spacer. J Med Microbiol. 2006;55:1349–55.PubMedCrossRefGoogle Scholar
  46. 46.
    Abdel-Rahman SM, Preuett B, Gaedigk A. Multi-locus genotyping identifies infections with multiple strains of Trichophyton tonsurans. J Clin Microbiol. 2007;45:1949–53.PubMedCrossRefGoogle Scholar
  47. 47.
    Shroba J, Olson-Burgess C, Preuett B, Abdel-Rahman SM. Molecular strain typing identifies a large outbreak of Trichophyton tonsurans among healthcare workers in a pediatric hospital. Am J Infect Contol. 2008 (in press).Google Scholar
  48. 48.
    Bhathena A, Gaedigk R, Abdel-Rahman SM. Characterization of the ALP1 gene locus of Trichophyton tonsurans. Mycopathologia. 2005;160:265–72.PubMedCrossRefGoogle Scholar
  49. 49.
    Chandrasekaran N, Kamalam A, Thambiah AS. Tinea capitis in an Anglo-Indian school. Trop Geogr Med. 1981;33:253–5.PubMedGoogle Scholar
  50. 50.
    Kamalam A, Thambiah AS. Trichophyton violaceum infection in an Indian school. Int J Dermatol. 1976;15:136–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Omar AA. Ringworm of the scalp in primary-school children in Alexandria: infection and carriage. East Mediterr Health J. 2000;6:961–7.PubMedGoogle Scholar
  52. 52.
    Awoderu VA, Nebo GC, Otudero VO. Occurrence of dermatomycoses and in-vitro therapeutic efficacy of three antifungal drugs on the growth of Epidermophyton floccosum. Mycopathologia. 2003;156:295–301.PubMedCrossRefGoogle Scholar
  53. 53.
    Lohoue Petmy J, Lando AJ, Kaptue L, Tchinda V, Folefack M. Superficial mycoses and HIV infection in Yaounde. J Eur Acad Dermatol Venereol. 2004;18:301–4.PubMedCrossRefGoogle Scholar
  54. 54.
    Woldeamanuel Y, Leekassa R, Chryssanthou E, Menghistu Y, Petrini B. Prevalence of tinea capitis in Ethiopian school children. Mycoses. 2005;48:137–41.PubMedCrossRefGoogle Scholar
  55. 55.
    Zaidi N, Konstantinou K, Zevros M. The role of molecular biology and nucleic acid technology in the study of human infection and epidemiology. Arch Pathol Lab Med. 2003;127:1098–105.PubMedGoogle Scholar
  56. 56.
    Cordeiro RA, Brilhante RSN, Rocha MFG, Rrabenhorsch SHB, Moreira JLB, Grangeiro TB, Sibrim JJC. Antifungal susceptibility and genetic similarity of sequential isolates of Trichophyton rubrum from an immunocompetent patient with chronic dermatophytosis. Clin Exp Dermatol. 2006;31:122–4.PubMedCrossRefGoogle Scholar
  57. 57.
    Mochizuki T, Tanabe H, Kawasaki M, Anzawa K, Ishizaki H. Survey of Trichophyton tonsurans infection in the Hokuriku and Kinki regions of Japan. Jpn J Med Mycol. 2005;46:99–103.Google Scholar
  58. 58.
    Mochizuki T, Tanabe H, Wakasa A, Kawasaki M, Anzawa K, Ishizaki H. Survey of Trichophyton tonsurans infection in Japan- molecular epidemiology and factors affecting adequate hairbrush sampling. Jpn J Med Mycol. 2006;47:57–61.CrossRefGoogle Scholar
  59. 59.
    Brilhante RSN, Rocha MFG, Cordeiro RA, Rabenhorst SHB, Granjeiro TB, Monteiro AJ, Sidrim JJC. Phenotypical and molecular characterization of Microsporum canis strains in north-east Brazil. J Appl Microbiol. 2005;99:776–82.PubMedCrossRefGoogle Scholar
  60. 60.
    Guoling Y, Xiaohong Y, Jingrong L, Liji J, Lijia A. A study on stability of phenotype and genotype of Trichophyton rubrum. Mycopathologia. 2006;161:205–12.PubMedCrossRefGoogle Scholar
  61. 61.
    Osborne CS, Leitner I, Favre B, Ryder NS. Amino acid substitution in Trichophyton rubrum squalene epoxidase associated with resistance to terbinafine. Antimicrob Agents Chemother. 2005;49:2840–4.PubMedCrossRefGoogle Scholar
  62. 62.
    Osborne CS, Leitner I, Hofbauer B, Fielding CA, Favre B, Ryder NS. Biological, biochemical, and molecular characterization of a new clinical Trichophyton rubrum isolate resistant to terbinafine. Antimicrob Agents Chemother. 2006;50:2234–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Bradley MC, Leidich S, Isham N, Elewski BE, Ghannoum MA. Antifungal susceptibilities and genetic relatedness of serial Trichophyton rubrum isolates from patients with onychomycosis of the toenail. Mycoses. 1999;42:105–10.PubMedGoogle Scholar
  64. 64.
    Brilhante RSN, Cordeiro RA, Medrano DJA, Monteiro AJ, Sidrim JJC, Rocha MFG. Antifungal susceptibility and genotypical pattern of Microsporum canis strains. Can J Microbiol. 2005;51:507–10.PubMedCrossRefGoogle Scholar
  65. 65.
    Nir-Paz R, Elinav H, Pierard GE, Walker D, Maly A, Shapiro M, Barton RC, Polacheck I. Deep infection of Trichophyton rubrum in an immunocompromised patient. J Clin Microbiol. 2003;41:5298–301.PubMedCrossRefGoogle Scholar
  66. 66.
    Kardjeva V, Summerbell R, Kantardjiev T, Devliotou-Panagiotidou D, Sotiriou E, Gräser Y. Forty-eight-hour diagnosis of onychomycosis with subtyping of Trichophyton rubrum strains. J Clin Microbiol. 2006;44:1419–27.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.Division of Pediatric Clinical PharmacologyThe Children’s Mercy Hospitals and ClinicsKansas CityUSA
  2. 2.Department of PediatricsUniversity of Missouri-Kansas City, School of MedicineKansas CityUSA

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