1887

Abstract

Dermatophytes are keratinophilic fungi that are the most common cause of fungal skin infections worldwide. Melanin has been isolated from several important human fungal pathogens, and the polymeric pigment is now recognized as an important virulence determinant. This study investigated whether dermatophytes, including , , and produce melanin or melanin-like compounds and during infection. Digestion of the pigmented microconidia and macroconidia of dermatophytes with proteolytic enzymes, denaturant and hot concentrated acid yielded dark particles that retained the size and shape of the original fungal cells. Electron spin resonance spectroscopy revealed that particles derived from pigmented conidia contained a stable free radical signal, consistent with the pigments being a melanin. Immunofluorescence analysis demonstrated reactivity of a melanin-binding mAb with the pigmented conidia and hyphae, as well as the isolate particles. Laccase, an enzyme involved in melanization, was detected in the dermatophytes by an agar plate assay using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as the substrate. Skin scrapings from patients with dermatophytoses contained septate hyphae and arthrospores that were reactive with the melanin-binding mAb. These findings indicate that dermatophytes can produce melanin or melanin-like compounds and during infection. Based on what is known about the function of melanin as a virulence factor of other pathogenic fungi, this pigment may have a similar role in the pathogenesis of dermatophytic diseases.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.047928-0
2011-08-01
2019-11-23
Loading full text...

Full text loading...

/deliver/fulltext/micro/157/8/2348.html?itemId=/content/journal/micro/10.1099/mic.0.047928-0&mimeType=html&fmt=ahah

References

  1. Ates A. , Ozcan K. , Ilkit M. . ( 2008; ). Diagnostic value of morphological, physiological and biochemical tests in distinguishing Trichophyton rubrum from Trichophyton mentagrophytes complex. . Med Mycol 46:, 811–822. [CrossRef].[PubMed].
    [Google Scholar]
  2. Brown D. W. , Hauser F. M. , Tommasi R. , Corlett S. , Salvo J. J. . ( 1993; ). Structural elucidation of a putative conidial pigment intermediate in Aspergillus parasiticus . . Tetrahedron Lett 34:, 419–422. [CrossRef]
    [Google Scholar]
  3. Butler M. J. , Day A. W. . ( 1998; ). Fungal melanins: a review. . Can J Microbiol 44:, 1115–1136.[CrossRef]
    [Google Scholar]
  4. Casadevall A. , Rosas A. L. , Nosanchuk J. D. . ( 2000; ). Melanin and virulence in Cryptococcus neoformans . . Curr Opin Microbiol 3:, 354–358. [CrossRef].[PubMed].
    [Google Scholar]
  5. Chai L. Y. , Netea M. G. , Sugui J. , Vonk A. G. , van de Sande W. W. , Warris A. , Kwon-Chung K. J. , Kullberg B. J. . ( 2010; ). Aspergillus fumigatus conidial melanin modulates host cytokine response. . Immunobiology 215:, 915–920. [CrossRef].[PubMed].
    [Google Scholar]
  6. Crowe J. D. , Olsson S. . ( 2001; ). Induction of laccase activity in Rhizoctonia solani by antagonistic Pseudomonas fluorescens strains and a range of chemical treatments. . Appl Environ Microbiol 67:, 2088–2094. [CrossRef].[PubMed].
    [Google Scholar]
  7. Cunha M. M. , Franzen A. J. , Seabra S. H. , Herbst M. H. , Vugman N. V. , Borba L. P. , de Souza W. , Rozental S. . ( 2010; ). Melanin in Fonsecaea pedrosoi: a trap for oxidative radicals. . BMC Microbiol 10:, 80–89. [CrossRef].[PubMed].
    [Google Scholar]
  8. Ellis D. , Marriott D. , Hajjeh R. A. , Warnock D. , Meyer W. , Barton R. . ( 2000; ). Epidemiology: surveillance of fungal infections. . Med Mycol 38: (Suppl. 1), 173–182.[PubMed].[CrossRef]
    [Google Scholar]
  9. Enochs W. S. , Nilges M. J. , Swartz H. M. . ( 1993; ). A standardized test for the identification and characterization of melanins using electron paramagnetic resonance (EPR) spectroscopy. . Pigment Cell Res 6:, 91–99. [CrossRef].[PubMed].
    [Google Scholar]
  10. Gómez B. L. , Nosanchuk J. D. , Díez S. , Youngchim S. , Aisen P. , Cano L. E. , Restrepo A. , Casadevall A. , Hamilton A. J. . ( 2001; ). Detection of melanin-like pigments in the dimorphic fungal pathogen Paracoccidioides brasiliensis in vitro and during infection. . Infect Immun 69:, 5760–5767. [CrossRef].[PubMed].
    [Google Scholar]
  11. Hiruma M. , Yamaguchi H. . ( 2003; ). Dermatophytes. . In Clinical Mycology, pp. 370–379. Edited by Anaissie E. J. , McGinnis M. R. , Pfaller M. A. . . The Curtis Center, PA:: Churchill Livingstone Press;.
    [Google Scholar]
  12. Jacobson E. S. . ( 2000; ). Pathogenic roles for fungal melanins. . Clin Microbiol Rev 13:, 708–717.[CrossRef]
    [Google Scholar]
  13. Jahn B. , Koch A. , Schmidt A. , Wanner G. , Gehringer H. , Bhakdi S. , Brakhage A. A. . ( 1997; ). Isolation and characterization of a pigmentless-conidium mutant of Aspergillus fumigatus with altered conidial surface and reduced virulence. . Infect Immun 65:, 5110–5117.[PubMed].
    [Google Scholar]
  14. Jahn B. , Boukhallouk F. , Lotz J. , Langfelder K. , Wanner G. , Brakhage A. A. . ( 2000; ). Interaction of human phagocytes with pigmentless Aspergillus conidia. . Infect Immun 68:, 3736–3739.[CrossRef]
    [Google Scholar]
  15. Jung H. , Xu F. , Li K. . ( 2002; ). Purification and characterization of laccase from wood-degrading fungus Trichophyton rubrum LKY-7. . Enzyme Microb Technol 30:, 161–168. [CrossRef]
    [Google Scholar]
  16. Kaben U. . ( 1967; ). [Dermatolycoses and dermatophyte flora in the adminission region of the university dermatological clinic of Rostock in the years 1961 to 1965 (with special consideration of Trichopyton rubrum species with melanoid pigment)]. . Dermatol Wochenschr 153:, 1112–1122 (in German).[PubMed].
    [Google Scholar]
  17. Langfelder K. , Jahn B. , Gehringer H. , Schmidt A. , Wanner G. , Brakhage A. A. . ( 1998; ). Identification of a polyketide synthase gene (pksP) of Aspergillus fumigatus involved in conidial pigment biosynthesis and virulence. . Med Microbiol Immunol (Berl) 187:, 79–89. [CrossRef].[PubMed].
    [Google Scholar]
  18. Liu S. , Tewari R. P. , Williamson P. R. . ( 1999; ). Laccase protects Cryptococcus neoformans from antifungal activity of alveolar macrophages. . Infect Immun 67:, 6034–6039.
    [Google Scholar]
  19. Mares D. , Romagnoli C. , Andreotti E. , Manfrini M. , Vicentini C. B. . ( 2004; ). Synthesis and antifungal action of new tricyclazole analogues. . J Agric Food Chem 52:, 2003–2009. [CrossRef].[PubMed].
    [Google Scholar]
  20. Marques S. A. , Robles A. M. , Tortorano A. M. , Tuculet M. A. , Negroni R. , Mendes R. P. . ( 2000; ). Mycoses associated with AIDS in the Third World. . Med Mycol 38: (Suppl. 1), 269–279.[PubMed].[CrossRef]
    [Google Scholar]
  21. Mednick A. J. , Nosanchuk J. D. , Casadevall A. . ( 2005; ). Melanization of Cryptococcus neoformans affects lung inflammatory responses during cryptococcal infection. . Infect Immun 73:, 2012–2019. [CrossRef].[PubMed].
    [Google Scholar]
  22. Morris-Jones R. , Youngchim S. , Gómez B. L. , Aisen P. , Hay R. J. , Nosanchuk J. D. , Casadevall A. , Hamilton A. J. . ( 2003; ). Synthesis of melanin-like pigments by Sporothrix schenckii in vitro and during mammalian infection. . Infect Immun 71:, 4026–4033. [CrossRef].[PubMed].
    [Google Scholar]
  23. Nosanchuk J. D. , Casadevall A. . ( 2003; ). The contribution of melanin to microbial pathogenesis. . Cell Microbiol 5:, 203–223.[CrossRef]
    [Google Scholar]
  24. Nosanchuk J. D. , Casadevall A. . ( 2006; ). Impact of melanin on microbial virulence and clinical resistance to antimicrobial compounds. . Antimicrob Agents Chemother 50:, 3519–3528. [CrossRef].[PubMed].
    [Google Scholar]
  25. Nosanchuk J. D. , Rosas A. L. , Lee S. C. , Casadevall A. . ( 2000; ). Melanisation of Cryptococcus neoformans in human brain tissue. . Lancet 355:, 2049–2050. [CrossRef].[PubMed].
    [Google Scholar]
  26. Nosanchuk J. D. , Ovalle R. , Casadevall A. . ( 2001; ). Glyphosate inhibits melanization of Cryptococcus neoformans and prolongs survival of mice after systemic infection. . J Infect Dis 183:, 1093–1099.[CrossRef]
    [Google Scholar]
  27. Nosanchuk J. D. , Gómez B. L. , Youngchim S. , Díez S. , Aisen P. , Zancopé-Oliveira R. M. , Restrepo A. , Casadevall A. , Hamilton A. J. . ( 2002; ). Histoplasma capsulatum synthesizes melanin-like pigments in vitro and during mammalian infection. . Infect Immun 70:, 5124–5131. [CrossRef].[PubMed].
    [Google Scholar]
  28. O’Hara E. B. , Timberlake W. E. . ( 1989; ). Molecular characterization of the Aspergillus nidulans yA locus. . Genetics 121:, 249–254.[PubMed].
    [Google Scholar]
  29. Perrin C. , Baran R. . ( 1994; ). Longitudinal melanonychia caused by Trichophyton rubrum. Histochemical and ultrastructural study of two cases. . J Am Acad Dermatol 31:, 311–316. [CrossRef].[PubMed].
    [Google Scholar]
  30. Pihet M. , Vandeputte P. , Tronchin G. , Renier G. , Saulnier P. , Georgeault S. , Mallet R. , Chabasse D. , Symoens F. , Bouchara J. P. . ( 2009; ). Melanin is an essential component for the integrity of the cell wall of Aspergillus fumigatus conidia. . BMC Microbiol 9:, 177–188. [CrossRef].[PubMed].
    [Google Scholar]
  31. Rodrigues M. L. , Nakayasu E. S. , Oliveira D. L. , Nimrichter L. , Nosanchuk J. D. , Almeida I. C. , Casadevall A. . ( 2008; ). Extracellular vesicles produced by Cryptococcus neoformans contain protein components associated with virulence. . Eukaryot Cell 7:, 58–67. [CrossRef].[PubMed].
    [Google Scholar]
  32. Romero-Martinez R. , Wheeler M. , Guerrero-Plata A. , Rico G. , Torres-Guerrero H. . ( 2000; ). Biosynthesis and functions of melanin in Sporothrix schenckii . . Infect Immun 68:, 3696–3703. [CrossRef].[PubMed].
    [Google Scholar]
  33. Rosas A. L. , Nosanchuk J. D. , Feldmesser M. , Cox G. M. , McDade H. C. , Casadevall A. . ( 2000; ). Synthesis of polymerized melanin by Cryptococcus neoformans in infected rodents. . Infect Immun 68:, 2845–2853. [CrossRef].[PubMed].
    [Google Scholar]
  34. Schönborn C. . ( 1971; ). Dermatophytes with melanoid pigment. 1. Occurrence of pigment-forming fungal strains and intensity of their pigment production. . Z Gesamte Hyg 17:, 773–778.
    [Google Scholar]
  35. Srinivasan C. , Dsouza T. M. , Boominathan K. , Reddy C. A. . ( 1995; ). Demonstration of laccase in the white rot Basidiomycete Phanerochaete chrysosporium BKM-F1767. . Appl Environ Microbiol 61:, 4274–4277.[PubMed].
    [Google Scholar]
  36. Tsai H. F. , Chang Y. C. , Washburn R. G. , Wheeler M. H. , Kwon-Chung K. J. . ( 1998; ). The developmentally regulated alb1 gene of Aspergillus fumigatus: its role in modulation of conidial morphology and virulence. . J Bacteriol 180:, 3031–3038.[PubMed].
    [Google Scholar]
  37. Tsai H. F. , Wheeler M. H. , Chang Y. C. , Kwon-Chung K. J. . ( 1999; ). A developmentally regulated gene cluster involved in conidial pigment biosynthesis in Aspergillus fumigatus . . J Bacteriol 181:, 6469–6477.[PubMed].
    [Google Scholar]
  38. Ungpakorn R. . ( 2005; ). Mycoses in Thailand: current concerns. . Nippon Ishinkin Gakkai Zasshi 46:, 81–86. [CrossRef].[PubMed].
    [Google Scholar]
  39. Wahleithner J. A. , Xu F. , Brown K. M. , Brown S. H. , Golightly E. J. , Halkier T. , Kauppinen S. , Pederson A. , Schneider P. . ( 1996; ). The identification and characterization of four laccases from the plant pathogenic fungus Rhizoctonia solani . . Curr Genet 29:, 395–403. [CrossRef].[PubMed].
    [Google Scholar]
  40. Walker G. C. , Milovanovic D. . ( 1970; ). Pigment formation in the dermatophytes. . Mycopathol Mycol Appl 42:, 369–379. [CrossRef].[PubMed].
    [Google Scholar]
  41. Wang Y. , Aisen P. , Casadevall A. . ( 1996; ). Melanin, melanin "ghosts," and melanin composition in Cryptococcus neoformans. . Infect Immun 64:, 2420–2424.
    [Google Scholar]
  42. Woo P. C. , Tam E. W. , Chong K. T. , Cai J. J. , Tung E. T. , Ngan A. H. , Lau S. K. , Yuen K. Y. . ( 2010; ). High diversity of polyketide synthase genes and the melanin biosynthesis gene cluster in Penicillium marneffei . . FEBS J 277:, 3750–3758. [CrossRef].[PubMed].
    [Google Scholar]
  43. Youngchim S. , Morris-Jones R. , Hay R. J. , Hamilton A. J. . ( 2004; ). Production of melanin by Aspergillus fumigatus . . J Med Microbiol 53:, 175–181. [CrossRef].[PubMed].
    [Google Scholar]
  44. Youngchim S. , Hay R. J. , Hamilton A. J. . ( 2005; ). Melanization of Penicillium marneffei in vitro and in vivo. . Microbiology 151:, 291–299. [CrossRef].[PubMed].
    [Google Scholar]
  45. Zhu X. , Gibbons J. , Garcia-Rivera J. , Casadevall A. , Williamson P. R. . ( 2001; ). Laccase of Cryptococcus neoformans is a cell wall-associated virulence factor. . Infect Immun 69:, 5589–5596. [CrossRef].[PubMed].
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.047928-0
Loading
/content/journal/micro/10.1099/mic.0.047928-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error