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Volume 153, Issue 12

laccase catalyses melanin synthesis from both - and -DOPA Free

Abstract

The human fungal pathogen produces melanin in the presence of various substrates, including the enantiomer of 3,4-dihydroxyphenylalanine (DOPA). The enzyme laccase catalyses the formation of melanin by oxidizing -DOPA, initiating a series of presumably spontaneous reactions that ultimately leads to the polymerization of the pigment in the yeast cell wall. There, melanin protects the cell from a multitude of environmental and host assaults. Thus, the ability of to produce pigments from a variety of available substrates is likely to confer a survival advantage. A number of isolates of different serotypes produced pigments from -DOPA, the stereoisomer of -DOPA. Acid-resistant particles were isolated from pigmented cells grown in the presence of -DOPA. Biophysical characterization showed the particles had a stably detectable free-radical signal by EPR, and negative zeta potential, similar to -DOPA-derived particles. No major differences were found between - and -DOPA ghosts in terms of binding to anti-melanin antibodies, or in overall architecture when imaged by electron microscopy. cells utilized - and -DOPA at a similar rate. Overall, our results indicate that shows little stereoselectivity for utilizing DOPA in melanin synthesis. The ability of to use both and enantiomers for melanization implies that this organism has access to a greater potential pool of substrates for melanin synthesis, and this could potentially be exploited in the design of therapeutic inhibitors of laccase.

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Keyword(s): DOPA, 3,4-dihydroxyphenylalanine
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2007-12-01
2024-04-19
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References

  1. Butler M. J., Day A. W. 1998; Fungal melanins: a review. Can J Microbiol 44:1115–1136
     [Google Scholar]
  2. Caldwell J. 1995; Stereochemical determinants of the nature and consequences of drug metabolism. J Chromatogr A 694:39–48
     [Google Scholar]
  3. Casadevall A., Steenbergen J. N., Nosanchuk J. D. 2003; ‘Ready made’ virulence and ‘dual use’ virulence factors in pathogenic environmental fungi – the Cryptococcus neoformans paradigm. Curr Opin Microbiol 6:332–337
     [Google Scholar]
  4. Chang Y. C., Kwon-Chung K. J. 1994; Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence. Mol Cell Biol 14:4912–4919
     [Google Scholar]
  5. Chaskes S., Casadevall A. 2006; Biochemical differentiation of Cryptococcus neoformans var. gattii from Cryptococcus neoformans var. on d-tryptophan d-proline agar. In American Society for Microbiology 106th General Meeting Orlando, FL:
     [Google Scholar]
  6. Chaskes S., Edberg S. C., Singer J. M. 1981; A dl-DOPA drop test for the identification of Cryptococcus neoformans . Mycopathologia 74:143–148
     [Google Scholar]
  7. da Silva M. B., Marques A. F., Nosanchuk J. D., Casadevall A., Travassos L. R., Taborda C. P. 2006; Melanin in the dimorphic fungal pathogen Paracoccidioides brasiliensis : effects on phagocytosis, intracellular resistance and drug susceptibility. Microbes Infect 8:197–205
     [Google Scholar]
  8. Doering T. L., Nosanchuk J. D., Roberts W. K., Casadevall A. 1999; Melanin as a potential cryptococcal defence against microbicidal proteins. Med Mycol 37:175–181
     [Google Scholar]
  9. Eisenman H. C., Nosanchuk J. D., Webber J. B., Emerson R. J., Camesano T. A., Casadevall A. 2005; Microstructure of cell wall-associated melanin in the human pathogenic fungus Cryptococcus neoformans . Biochemistry 44:3683–3693
     [Google Scholar]
  10. 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
     [Google Scholar]
  11. Espin J. C., Garcia-Ruiz P. A., Tudela J., Garcia-Canovas F. 1998; Study of stereospecificity in mushroom tyrosinase. Biochem J 331:547–551
     [Google Scholar]
  12. Frases S., Chaskes S., Dadachova E., Casadevall A. 2006; Induction by Klebsiella aerogenes of a melanin-like pigment in Cryptococcus neoformans . Appl Environ Microbiol 72:1542–1550
     [Google Scholar]
  13. Frases S., Salazar A., Dadachova E., Casadevall A. 2007; Cryptococcus neoformans can utilize the bacterial melanin precursor homogentisic acid for fungal melanogenesis. Appl Environ Microbiol 73:615–621
     [Google Scholar]
  14. Garcia-Rivera J., Eisenman H. C., Nosanchuk J. D., Aisen P., Zaragoza O., Moadel T., Dadachova E., Casadevall A. 2005; Comparative analysis of Cryptococcus neoformans acid-resistant particles generated from pigmented cells grown in different laccase substrates. Fungal Genet Biol 42:989–998
     [Google Scholar]
  15. Glatman-Freedman A., Martin J. M., Riska P. F., Bloom B. R., Casadevall A. 1996; Monoclonal antibodies to surface antigens of Mycobacterium tuberculosis and their use in a modified enzyme-linked immunosorbent spot assay for detection of mycobacteria. J Clin Microbiol 34:2795–2802
     [Google Scholar]
  16. Hicks J. K., D'Souza C. A., Cox G. M., Heitman J. 2004; Cyclic AMP-dependent protein kinase catalytic subunits have divergent roles in virulence factor production in two varieties of the fungal pathogen Cryptococcus neoformans . Eukaryot Cell 3:14–26
     [Google Scholar]
  17. Kahn V., Pomerantz S. H. 1980; Monophenolase activity of avocado polyphenol oxidase. Phytochemistry 19:379–385
     [Google Scholar]
  18. Kwon-Chung K. J., Varma A. 2006; Do major species concepts support one, two or more species within Cryptococcus neoformans ?. FEMS Yeast Res 6:574–587
     [Google Scholar]
  19. Kwon-Chung K. J., Tom W. K., Costa J. L. 1983; Utilization of indole compounds by Cryptococcus neoformans to produce a melanin-like pigment. J Clin Microbiol 18:1419–1421
     [Google Scholar]
  20. Lamzin V. S., Dauter Z., Wilson K. S. 1995; How nature deals with stereoisomers. Curr Opin Struct Biol 5:830–836
     [Google Scholar]
  21. Nosanchuk J. D., Casadevall A. 1997; Cellular charge of Cryptococcus neoformans : contributions from the capsular polysaccharide, melanin, and monoclonal antibody binding. Infect Immun 65:1836–1841
     [Google Scholar]
  22. Nosanchuk J. D., Casadevall A. 2003; The contribution of melanin to microbial pathogenesis. Cell Microbiol 5:203–223
     [Google Scholar]
  23. 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
     [Google Scholar]
  24. Perfect J. R., Casadevall A. 2002; Cryptococcosis. Infect Dis Clin North Am 16:837–874 v–vi
    [Google Scholar]
  25. Polacheck I., Hearing V. J., Kwon-Chung K. J. 1982; Biochemical studies of phenoloxidase and utilization of catecholamines in Cryptococcus neoformans . J Bacteriol 150:1212–1220
     [Google Scholar]
  26. Polacheck I., Platt Y., Aronovitch J. 1990; Catecholamines and virulence of Cryptococcus neoformans . Infect Immun 58:2919–2922
     [Google Scholar]
  27. Pomerantz S. H. 1963; Separation, purification, and properties of two tyrosinases from hamster melanoma. J Biol Chem 238:2351–2357
     [Google Scholar]
  28. Prabhakaran K., Harris E. B., Kirchheimer W. F. 1972; The nature of the phenolase enzyme in Mycobacterium leprae : structure–activity relationships of substrates and comparison with other copper proteins and enzymes. Microbios 5:273–281
     [Google Scholar]
  29. Richmond D. V., Fisher D. J. 1973; The electrophoretic mobility of micro-organisms. Adv Microb Physiol 9:1–29
     [Google Scholar]
  30. Riley P. A. 1997; Melanin. Int J Biochem Cell Biol 29:1235–1239
     [Google Scholar]
  31. Rosas A. L., Nosanchuk J. D., Feldmesser M., Cox G. M., McDade H. C., Casadevall A. 2000a; Synthesis of polymerized melanin by Cryptococcus neoformans in infected rodents. Infect Immun 68:2845–2853
     [Google Scholar]
  32. Rosas A. L., Nosanchuk J. D., Gomez B. L., Edens W. A., Henson J. M., Casadevall A. 2000b; Isolation and serological analyses of fungal melanins. J Immunol Methods 244:69–80
     [Google Scholar]
  33. Rose I. A. 1972; Enzyme reaction stereospecificity: a critical review. CRC Crit Rev Biochem 1:33–57
     [Google Scholar]
  34. Salas S. D., Bennett J. E., Kwon-Chung K. J., Perfect J. R., Williamson P. R. 1996; Effect of the laccase gene CNLAC1 , on virulence of Cryptococcus neoformans . J Exp Med 184:377–386
     [Google Scholar]
  35. Schnitzler N., Peltroche-Llacsahuanga H., Bestier N., Zundorf J., Lutticken R., Haase G. 1999; Effect of melanin and carotenoids of Exophiala ( Wangiella ) dermatitidis on phagocytosis, oxidative burst, and killing by human neutrophils. Infect Immun 67:94–101
     [Google Scholar]
  36. Steenbergen J. N., Shuman H. A., Casadevall A. 2001; Cryptococcus neoformans interactions with amoebae suggest an explanation for its virulence and intracellular pathogenic strategy in macrophages. Proc Natl Acad Sci U S A 98:15245–15250
     [Google Scholar]
  37. Wang Y., Aisen P., Casadevall A. 1995; Cryptococcus neoformans melanin and virulence: mechanism of action. Infect Immun 63:3131–3136
     [Google Scholar]
  38. Williamson P. R. 1994; Biochemical and molecular characterization of the diphenol oxidase of Cryptococcus neoformans : identification as a laccase. J Bacteriol 176:656–664
     [Google Scholar]
  39. Williamson P. R. 1997; Laccase and melanin in the pathogenesis of Cryptococcus neoformans . Front Biosci 2:e99–e107
     [Google Scholar]
  40. 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
     [Google Scholar]
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Cryptococcus neoformans laccase catalyses melanin synthesis from both d- and l-DOPA
Microbiology 153, 3954 (2007); https://doi.org/10.1099/mic.0.2007/011049-0
/content/journal/micro/10.1099/mic.0.2007/011049-0
/content/journal/micro/10.1099/mic.0.2007/011049-0
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