Fungi that infect humans are a major health problem, especially for those with compromised immune systems. Many fungal infections are extremely difficult to cure and if left untreated are fatal. For successful infection to occur, the fungal pathogen must be able to grow by acquiring and utilising the available nutrient sources within the host whilst evading or tolerating the host’s defence systems. Expression profiling in several pathogenic fungal species has revealed that genes required for tyrosine catabolism are induced specifically in the pathogenic cell type at 37°C. As well as enabling the fungus to acquire carbon and nitrogen intermediates from proteins within the host, tyrosine is also an important precursor in the formation of two different types of melanin, which protects cells against the host’s defence systems. This study shows that the ability to catabolise tyrosine and produce tyrosine derived melanin is not required for the initial stages of fungal infection. However, a novel role for hpdA, which encodes the enzyme which catalyses the second step of tyrosine catabolism, was identified during growth in host cells.
Vyšlo v časopise: Intracellular Growth Is Dependent on Tyrosine Catabolism in the Dimorphic Fungal Pathogen. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004790 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004790
1. Lorenz MC, Fink GR (2002) Life and death in a macrophage: role of the glyoxylate cycle in virulence. Eukaryot Cell 1 : 657–662. 12455685
2. Nunes LR, Costa de Oliveira R, Leite DB, Schmidt da Silva V, doa Reis Marques E, et al. (2005) Transcriptome analysis of Paracoccidioides brasiliensis cells undergoing mycelium-to-yeast transition. Eukaryot Cell 4 : 2115–2128. 16339729
3. Fan W, Kraus PR, Boily MJ, Heitman J (2005) Cryptococcus neoformans gene expression during murine macrophage infection. Eukaryot Cell 4 : 1420–1433. 16087747
4. Hwang L, Hocking-Maurray D, Bahramai AK, Andersson M, Rine J, et al. (2003) Identifying phase-specific genes in the fungal pathogen Histoplasma capsulatum using a genomic shotgun microarray. Mol Biol Cell 14 : 2314–2326. 12808032
5. Keller S, Macheleidt J, Scherlach K, Schmaler-Ripcke J, Jacobsen ID, et al. (2011) Pyomelanin formation in Aspergillus fumigatus requires HmgX and the transcriptional activator HmgR but is dispensable for virulence. PLoS One 6: e26604. doi: 10.1371/journal.pone.0026604 22046314
6. Pasricha S, Payne M, Canovas D, Pase L, Ngaosuwankul N, et al. (2013) Cell-type-specific transcriptional profiles of the dimorphic pathogen Penicillium marneffei reflect distinct reproductive, morphological, and environmental demands. G3 (Bethesda) 3 : 1997–2014.
7. Fernandez-Canon JM, Penalva MA (1995) Fungal metabolic model for human type I hereditary tyrosinaemia. PNAS 92 : 9132–9136. 7568087
8. Penalva MA (2001) A fungal perspective on human inborn errors of metabolism: alkaptonuria and beyond. Fungal Genet Biol 34 : 1–10. 11567547
9. Langfelder K, Streibel M, Jahn B, Haase G, Brakhage AA (2003) Biosynthesis of fungal melanins and their importance for human pathogenic fungi. Fungal Genet Biol 38 : 143–158. 12620252
10. Fernandez-Canon JM, Penalva MA (1995) Molecular characterization of a gene encoding a homogentisate dioxygenase from Aspergillus nidulans and identification of its human and plant homologues. J Biol Chem 270 : 21199–21205. 7673153
11. Schmaler-Ripcke J, Sugareva V, Gebhardt P, Winkler R, Kniemeyer O, et al. (2009) Production of pyomelanin, a second type of melanin, via the tyrosine degradation pathway in Aspergillus fumigatus. Appl Environ Microbiol 75 : 493–503. doi: 10.1128/AEM.02077-08 19028908
12. Kwon-Chung KJ, Polacheck I, Popkin TJ (1982) Melanin-lacking mutants of Cryptococcus neoformans and their virulence for mice. J Bact 150 : 1414–1421. 6804444
13. Wang Y, Casadevall A (1994) Susceptibility of melanized and nonmelanized Cryptococcus neoformans to nitrogen - and oxygen - derived oxidants. Infect Immun 62 : 3004–3007. 8005689
14. Dixon DM, Polak A, Szaniszlo PJ (1987) Pathogenicity and virulence of wild-type and melanin-deficient Wangiella dermatitidis. J Med Vet Mycol 25 : 97–106. 3598824
15. Jahn B, Koch A, Schmidt A, Wanner G, Gehringer H, et al. (1997) Isolation and characterization of a pigmentless-conidium mutant of Aspergillus fumigatus with altered connidial surface and reduced virulence. Infect Immun 65 : 5110–5117. 9393803
16. Woo PC, Tam EW, Chong KT, Cai JJ, Tung ET, et al. (2010) High diversity of polyketide synthase genes and the melanin biosynthesis gene cluster in Penicillium marneffei. Febs J 277 : 3750–3758. doi: 10.1111/j.1742-4658.2010.07776.x 20718860
17. Mednick AJ, Nosanchuk JD, Casadevall A (2005) Melanization of Cryptococcus neoformans affects lung inflammatory responses during cryptococcal infection. Infect Immun 73 : 2012–2019. 15784542
18. da Silva MB, Marques AF, Nosanchuk JD, Casadevall A, Travassos LR, et al. (2006) Melanin in the dimorphic fungal pathogen Paracoccidioides brasiliensis: effects on phagocytosis, intracellular resistance and drug susceptibility. Microbes Infect 8 : 197–205. 16213179
19. 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. 10816530
20. Jahn B, Boukhallouk F, Lotz J, Langfelder K, Wanner G, et al. (2000) Interaction of human phagocytes with pigmentless Aspergillus conidia. Infect Immun 68 : 3736–3739. 10816538
21. Jahn B, Langfelder K, Schneider U, Schindel C, Brakhage AA (2002) PKSP-dependent reduction of phagolysosome fusion and intracellular kill of Aspergillus fumigatus conidia by human monocyte-derived macrophages. Cell Microbiol 4 : 793–803. 12464010
22. Huffnagle GB, Chen GH, Curtis JL, McDonald RA, Strieter RM, et al. (1995) Down-regulation of the afferent phase of T cell-mediated pulmonary inflammation and immunity by a high melanin-producing strain of Cryptococcus neoformans. J Immunol 155 : 3507–3516. 7561046
23. Youngchim S, Hay RJ, Hamilton AJ (2005) Melanization of Penicillium marneffei in vitro and in vivo. Micrbiology 151 : 291–299. 15632446
24. Taborda CP, da Silva MB, Nosanchuk JD, Travassos LR (2008) Melanin as a virulence factor of Paracoccidioides brasiliensis and other dimorphic pathogenic fungi: a minireview. Mycopathologia 165 : 331–339. 18777637
25. Gomez BL, Nosanchuk JD, Diez S, Youngchim S, Aisen P, et al. (2001) Detection of melanin-like pigments in the dimorphic fungal pathogen Paracoccidioides brasiliensis in vitro and during infection. Infect Immun 69 : 5760–5767. 11500453
26. Nosanchuk JD, Gomez BL, Youngchim S, Diez S, Aisen P, et al. (2002) Histoplasma capsulatum synthesizes melanin-like pigments in vitro and during mammalian infection. Infect Immun 70 : 5124–5131. 12183562
27. Keon J, Hargreaves J (1998) Isolation and heterologous expression of a gene encoding 4-hydroxyphenylpyruvate dioxygenase from the wheat leaf-spot pathogen, Mycosphaerella graminicola. FEMS Microbiol Lett 161 : 337–343. 9570125
28. Lock EA, Ellis MK, Gaskin P, Robinson M, Auton TR, et al. (1998) From toxicological problem to therapeutic use: the discovery of the mode of action of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), its toxicology and development as a drug. J Inherit Metab Dis 21 : 498–506. 9728330
29. Marzluf GA (1997) Genetic regulation of nitrogen metabolism in the fungi. Microbiol Mol Biol Rev 61 : 17–32. 9106362
30. Bugeja HE, Hynes MJ, Andrianopoulos A (2012) AreA controls nitrogen source utilisation during both growth programs of the dimorphic fungus Penicillium marneffei. Fungal Biol 116 : 145–154. doi: 10.1016/j.funbio.2011.10.009 22208609
31. Rodriguez-Rojas A, Mena A, Martin S, Borrell N, Oliver A, et al. (2009) Inactivation of the hmgA gene of Pseudomonas aeruginosa leads to pyomelanin hyperproduction, stress resistance and increased persistence in chronic lung infection. Microbiology 155 : 1050–1057. doi: 10.1099/mic.0.024745-0 19332807
32. da Silva Ferreira ME, Savoldi M, Sueli Bonato P, Goldman MH, Goldman GH (2006) Fungal metabolic model for tyrosinemia type 3: molecular characterization of a gene encoding a 4-hydroxy-phenyl pyruvate dioxygenase from Aspergillus nidulans. Eukaryot Cell 5 : 1441–1445. 16896227
33. Fernandez-Canon JM, Penalva MA (1998) Characterization of a fungal maleylacetoacetate isomerase gene and identification of its human homologue. J Biol Chem 273 : 329–337. 9417084
34. Sharma KK, Arst HN Jr. (1985) The product of the regulatory gene of the proline catabolism gene cluster of Aspergillus nidulans is a positive-acting protein. Curr Genet 9 : 299–304. 3916725
35. Empel J, Sitkiewicz I, Andrukiewicz A, Lasocki K, Borsuk P, et al. (2001) arcA, the regulatory gene for the arginine catabolic pathway in Aspergillus nidulans. Mol Genet Genomics 266 : 591–597. 11810230
36. Berger H, Basheer A, Bock S, Reyes-Dominguez Y, Dalik T, et al. (2008) Dissecting individual steps of nitrogen transcription factor cooperation in the Aspergillus nidulans nitrate cluster. Mol Microbiol 69 : 1385–1398. doi: 10.1111/j.1365-2958.2008.06359.x 18673441
37. Gournas C, Oestreicher N, Amillis S, Diallinas G, Scazzocchio C (2011) Completing the purine utilisation pathway of Aspergillus nidulans. Fungal Genet Biol 48 : 840–848. doi: 10.1016/j.fgb.2011.03.004 21419234
38. Miller BL, Miller KY, Roberti KA, Timberlake WE (1987) Position-dependent and -independent mechanisms regulate cell-specific expression of the SpoC1 gene cluster of Aspergillus nidulans. Mol Cell Biol 7 : 427–434. 3550422
39. Hynes MJ (1975) Studies on the role of the areA gene in the regulation of nitrogen catabolism in Aspergillus nidulans. Aust J Biol Sci 28 : 301–313. 52352
40. Hawker KL, Montague P, Kinghorn JR (1992) Nitrate reductase and nitrite reductase transcript levels in various mutants of Aspergillus nidulans: confirmation of autogenous regulation. Mol Gen Genet 231 : 485–488. 1538701
41. Oestreicher N, Ribard C, Scazzocchio C (2008) The nadA gene of Aspergillus nidulans, encoding adenine deaminase, is subject to a unique regulatory pattern. Fungal Genet Biol 45 : 760–775. 18055231
42. Welch JJ, Watts JA, Vakoc CR, Yao Y, Wang H, et al. (2004) Global regulation of erythroid gene expression by transcription factor GATA-1. Blood 104 : 3136–3147. 15297311
43. Macios M, Caddick MX, Weglenski P, Scazzocchio C, Dzikowska A (2012) The GATA factors AREA and AREB together with the co-repressor NMRA, negatively regulate arginine catabolism in Aspergillus nidulans in response to nitrogen and carbon source. Fungal Genet Biol 49 : 189–198. doi: 10.1016/j.fgb.2012.01.004 22300944
44. Fu L, Dong SS, Xie YW, Tai LS, Chen L, Kong KL, Man K, Xie D, Li Y, Cheng Y, Tao Q, Guan XY (2010) Down-regulation of tyrosine aminotransferase at a frequently deleted region 16q22 contributes to the pathogenesis of hepatocellular carcinoma. Hepatology 51 : 1624–1634. doi: 10.1002/hep.23540 20209601
45. Lee SS, Kennedy S, Tolonen AC, Ruvkun G (2003) DAF-16 target genes that control C. elegans life-span and metabolism. Science 300 : 644–647. 12690206
46. Ferguson AA, Roy S, Kormanik KN, Kim Y, Dumas KJ, Ritov VB, Matern D, Hu PJ, Fisher AL (2013) TATN-1 mutations reveal a novel role for tyrosine as a metabolic signal that influences developmental decisions and longevity in Caenorhabditis elegans. PLoS Genet 9: e1004020. doi: 10.1371/journal.pgen.1004020 24385923
47. Finch CE, Ruvkun G (2001) The genetics of aging. Annu Rev Genomics Hum Genet 2 : 435–462. 11701657
48. Borneman AR, Hynes MJ, Andrianopoulos A (2000) The abaA homologue of Penicillium marneffei participates in two developmental programmes: conidiation and dimorphic growth. Mol Microbiol 38 : 1034–1047. 11123677
49. Sambrook J, Fritsch EF, Maniatis T (1989) Molecular Cloning, A Laboratory Manual. Cold Spring Harbor, USA: Cold Spring Harbor Laboratory Press.
50. Bugeja HE, Boyce KJ, Weerasinghe H, Beard S, Jeziorowski A, et al. (2012) Tools for high efficiency genetic manipulation of the human pathogen Penicillium marneffei. Fungal Genet Biol 49 : 772–778. doi: 10.1016/j.fgb.2012.08.003 22921264
51. Ausubel FM, Brent R, Kingston RE, Moore RE, Seidman JA, et al. (1994) Current protocols in molecular biology. New York: John Wiley and Sons, Inc.
52. Cove DJ, Quatrano RS, Hartmann E (1996) The alignment of the axis of asymmetry in regenerating protoplasts of the moss, Ceratodon purpureus, is determined independently of axis polarity. Development 122 : 371–379. 8565849
Zvýšte si kvalifikáciu online z pohodlia domova
Nemáte účet? Registrujte sa
Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
