The mtfA transcription factor gene controls morphogenesis, gliotoxin production, and virulence in the opportunistic human pathogen Aspergillus fumigatus

Eukaryotic Cell

Volumn 13, Issue 6, 2014, Pages 766-775

  Smith, Timothy D ^a   Calvo, Ana M ^a  

^a NORTHERN ILLINOIS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FUNGAL PROTEIN; GLIOTOXIN; PEPTIDE HYDROLASE; TRANSCRIPTION FACTOR; VIRULENCE FACTOR;

ASPERGILLUS NIDULANS; BIOSYNTHESIS; FUNGUS SPORE; GENETICS; GROWTH, DEVELOPMENT AND AGING; METABOLISM; PATHOGENICITY; VIRULENCE;

ASPERGILLUS NIDULANS; FUNGAL PROTEINS; GLIOTOXIN; PEPTIDE HYDROLASES; SPORES, FUNGAL; TRANSCRIPTION FACTORS; VIRULENCE; VIRULENCE FACTORS;

EID: 84901477603     PISSN: 15359778     EISSN: None     Source Type: Journal    
DOI: 10.1128/EC.00075-14     Document Type: Article

References (70)

1. Osherov N. 2012. Interaction of the pathogenic mold fungus Aspergillus fumigatus with lung epithelial cells. Front. Microbiol. 3: 346. http://dx.doi.org/10.3389/fmicb.2012.00346.
2. Knutsen AP, Slavin RG. 2011. Allergic bronchopulmonary aspergillosis in asthma and cystic fibrosis. Clin. Dev. Immunol. 2011: 843763. http://dx.doi.org/10.1155/2011/843763.
3. Denning DW. 1998. Invasive aspergillosis. Clin. Infect. Dis. 26: 781-803. http://dx.doi.org/10.1086/513943.
4. Kliasova GA, Petrova NA, Parovichnikova EN, Gotman LN, Isaev VG, Mikhailova EA, Ustinova EN, Khoroshko ND, Vishnevskaia ES, Kremenetskaia AM, Kravchenko SK, Kaplanskaia IB, Kokhno AA, Ptitsin SA, Liubimova LS, Mendeleeva LP, Mitish NE, Galstian GM, Ryzhko W, Tochenov AV, Savchenko VG. 2005. Invasive pulmonary aspergillosis. Ter. Ark. 77: 65-71.
5. Marr KA, Carter RA, Boeckh M, Martin P, Corey L. 2002. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood 100: 4358-4366. http://dx.doi.org/10.1182/blood-2002-05-1496.
6. Pagano L, Girmenia C, Mele L, Ricci P, Tosti ME, Nosari A, Buelli M, Picardi M, Allione B, Corvatta L, D'Antonio D, Montillo M, Melillo L, Chierichini A, Cenacchi A, Tonso A, Cudillo L, Candoni A, Savignano C, Bonini A, Martino P, Del Favero A. 2001. Infections caused by filamentous fungi in patients with hematologic malignancies. A report of 391 cases by GIMEMA Infection Program. Haematologica 86: 862-870.
7. Post MJ, Lass-Floerl C, Gastl G, Nachbaur D. 2007. Invasive fungal infections in allogeneic and autologous stem cell transplant recipients: a single-center study of 166 transplanted patients. Transpl. Infect. Dis. 9: 189-195. http://dx.doi.org/10.1111/j.1399-3062.2007.00219.x.
8. Wiederhold NP, Lewis RE. 2003. Invasive aspergillosis in patients with hematologic malignancies. Pharmacotherapy 23: 1592-1610. http://dx.doi.org/10.1592/phco.23.15.1592.31965.
9. Latge JP. 1999. Aspergillus fumigatus and aspergillosis. Clin. Microbiol. Rev. 12: 310-350.
10. Hohl TM, Feldmesser M. 2007. Aspergillus fumigatus: principles of pathogenesis and host defense. Eukaryot. Cell 6: 1953-1963. http://dx.doi.org/10.1128/EC.00274-07.
11. Sherif R, Segal BH. 2010. Pulmonary aspergillosis: clinical presentation, diagnostic tests, management and complications. Curr. Opin. Pulm. Med. 16: 242-250. http://dx.doi.org/10.1097/MCP.0b013e328337d6de.
12. Ruchel R, Reichard U. 1999. Pathogenesis and clinical presentation of aspergillosis. Contrib. Microbiol. 2: 21-43. http://dx.doi.org/10.1159/000060302.
13. Cunha C, Di Ianni M, Bozza S, Giovannini G, Zagarella S, Zelante T, D'Angelo C, Pierini A, Pitzurra L, Falzetti F, Carotti A, Perruccio K, Latge JP, Rodrigues F, Velardi A, Aversa F, Romani L, Carvalho A. 2010. Dectin-1 Y238X polymorphism associates with susceptibility to invasive aspergillosis in hematopoietic transplantation through impairment of both recipient-and donor-dependent mechanisms of antifungal immunity. Blood 116: 5394-5402. http://dx.doi.org/10.1182/blood-2010-04-279307.
14. Sun WK, Lu X, Li X, Sun QY, Su X, Song Y, Sun HM, Shi Y. 6 May 2012. Dectin-1 is inducible and plays a crucial role in Aspergillus-induced innate immune responses in human bronchial epithelial cells. Eur. J. Clin. Microbiol. Infect. Dis. http://dx.doi.org/10.1007/s10096-012-1624-8.
15. Calvo AM, Wilson RA, Bok JW, Keller NP. 2002. Relationship between secondary metabolism and fungal development. Microbiol. Mol. Biol. Rev. 66: 447-459. http://dx.doi.org/10.1128/MMBR.66.3.447-459.2002.
16. Calvo AM. 2008. The VeA regulatory system and its role in morphological and chemical development in fungi. Fungal Genet. Biol. 45: 1053-1061. http://dx.doi.org/10.1016/j.fgb.2008.03.014.
17. Dhingra S, Andes D, Calvo AM. 2012. VeA regulates conidiation, gliotoxin production, and protease activity in the opportunistic human pathogen Aspergillus fumigatus. Eukaryot. Cell 11: 1531-1543. http://dx.doi.org/10.1128/EC.00222-12.
18. Park H, Bayram O, Braus G, Kim SC, Yu J. 2012. Characterization of the velvet regulators in Aspergillus fumigatus. Mol. Microbiol. 86: 937-953. http://dx.doi.org/10.1111/mmi.12032.
19. Tekaia F, Latge JP. 2005. Aspergillus fumigatus: saprophyte or pathogen? Curr. Opin. Microbiol. 8: 385-392. http://dx.doi.org/10.1016/j.mib.2005.06.017.
20. Amitani R, Taylor G, Elezis EN, Llewellyn-Jones C, Mitchell J, Kuze F, Cole PJ, Wilson R. 1995. Purification and characterization of factors produced by Aspergillus fumigatus which affect human ciliated respiratory epithelium. Infect. Immun. 63: 3266-3271.
21. Bok JW, Chung D, Balajee SA, Marr KA, Andes D, Nielsen KF, Frisvad JC, Kirby KA, Keller NP. 2006. GliZ, a transcriptional regulator of gliotoxin biosynthesis, contributes to Aspergillus fumigatus virulence. Infect. Immun. 74: 6761-6768. http://dx.doi.org/10.1128/IAI.00780-06.
22. Comera C, André K, Laffitte J, Collet X, Galtier P, Maridonneau-Parini I. 2007. Gliotoxin from Aspergillus fumigatus affects phagocytosis and the organization of the actin cytoskeleton by distinct signaling pathways in human neutrophils. Microbes Infect. 9: 47-54. http://dx.doi.org/10.1016/j.micinf.2006.10.009.
23. Frame R, Carlton WW. 1988. Acute toxicity of gliotoxin in hamsters. Toxicol. Lett. 40: 269-273. http://dx.doi.org/10.1016/0378-4274(88)90050-1.
24. Mullbacher A, Eichner RD. 1984. Immunosuppression in vitro by a metabolite of a human pathogenic fungus. Proc. Natl. Acad. Sci. U. S. A. 81: 3835-3837. http://dx.doi.org/10.1073/pnas.81.12.3835.
25. Pan XQ, Harday J. 2007. Electromicroscopic observations on gliotoxininduced apoptosis of cancer cells in culture and human cancer xenografts in transplanted SCID mice. In Vivo 21: 259-265.
26. Piva TJ. 1994. Gliotoxin induces apoptosis in mouse l929 fibroblast cells. Biochem. Mol. Biol. Int. 33: 411-419.
27. Stanzani M, Orciuolo E, Lewis R, Kontoyiannis DP, Martins SL, St John LS, Komanduri KV. 2005. Aspergillus fumigatus suppresses the human cellular immune response via gliotoxin-mediated apoptosis of monocytes. Blood 105: 2258-2265. http://dx.doi.org/10.1182/blood-2004-09-3421.
28. Suen YK, Fung KP, Lee CY, Kong SK. 2001. Gliotoxin induces apoptosis in cultured macrophages via production of reactive oxygen species and cytochrome c release without mitochondrial depolarization. Free Radic. Res. 35: 1-10. http://dx.doi.org/10.1080/10715760100300541.
29. Tsunawaki S, Yoshida LS, Nishida S, Kobayashi T, Shimoyama T. 2004. Fungal metabolite gliotoxin inhibits assembly of the human respiratory burst NADPH oxidase. Infect. Immun. 72: 3373-3382. http://dx.doi.org/10.1128/IAI.72.6.3373-3382.2004.
30. Waring P. 1990. DNA fragmentation induced in macrophages by gliotoxin does not require protein-synthesis and is preceded by raised inositol triphosphate levels. J. Biol. Chem. 265: 14476-14480.
31. Yamada A, Kataoka T, Nagai K. 2000. The fungal metabolite gliotoxin: immunosuppressive activity on CTL-mediated cytotoxicity. Immunol. Lett. 71: 27-32. http://dx.doi.org/10.1016/S0165-2478(99)00155-8.
32. Yoshida LS, Abe S, Tsunawaki S. 2000. Fungal gliotoxin targets the onset of superoxide-generating NADPH oxidase of human neutrophils. Biochem. Biophys. Res. Commun. 268: 716-723. http://dx.doi.org/10.1006/bbrc.2000.2192.
33. Eichner RD, Waring P, Geue AM, Braithwaite AW, Mullbacher A. 1988. Gliotoxin causes oxidative damage to plasmid and cellular DNA. J. Biol. Chem. 263: 3772-3777.
34. Richard JL, Dvorak TJ, Ross PF. 1996. Natural occurrence of gliotoxin in turkeys infected with Aspergillus fumigatus, Fresenius. Mycopathologia 134: 167-170. http://dx.doi.org/10.1007/BF00436725.
35. Dhingra S, Lind AL, Lin HC, Tang Y, Rokas A, Calvo AM. 2013. The fumagillin gene cluster, an example of hundreds of genes under veA control in Aspergillus fumigatus. PLoS One 8: e77147. http://dx.doi.org/10.1371/journal.pone.0077147.
36. Stinnett SM, Espeso EA, Cobeno L, Araujo-Bazan L, Calvo AM. 2007. Aspergillus nidulans VeA subcellular localization is dependent on the importin alpha carrier and on light. Mol. Microbiol. 63: 242-255. http://dx.doi.org/10.1111/j.1365-2958.2006.05506.x.
37. Kato N, Brooks W, Calvo AM. 2003. The expression of sterigmatocystin and penicillin genes in Aspergillus nidulans is controlled by veA, a gene required for sexual development. Eukaryot. Cell 2: 1178-1186. http://dx.doi.org/10.1128/EC.2.6.1178-1186.2003.
38. Bayram O, Krappmann S, Ni M, Bok JW, Helmstaedt K, Valerius O, Braus-Stromeyer S, Kwon NJ, Keller NP, Yu JH, Braus GH. 2008. VelB/VeA/LaeA complex coordinates light signal with fungal development and secondary metabolism. Science 320: 1504-1506. http://dx.doi.org/10.1126/science.1155888.
39. Bayram O, Braus GH. 2012. Coordination of secondary metabolism and development in fungi: the velvet family of regulatory proteins. FEMS Microbiol. Rev. 36: 1-24. http://dx.doi.org/10.1111/j.1574-6976.2011.00285.x.
40. Ramamoorthy V, Dhingra S, Kincaid A, Shantappa S, Feng X, Calvo AM. 2013. The putative C2H2 transcription factor MtfA is a novel regulator of secondary metabolism and morphogenesis in Aspergillus nidulans. PLoS One 8: e74122. http://dx.doi.org/10.1371/journal.pone.0074122.
41. Käfer E. 1977. Meiotic and mitotic recombination in Aspergillus and its chromosomal aberrations. Adv. Genet. 19: 33-131. http://dx.doi.org/10.1016/S0065-2660(08)60245-X.
42. Szewczyk E, Nayak T, Oakley CE, Edgerton H, Xiong Y, Taheri-Talesh N, Osmani SA, Oakley BR. 2006. Fusion PCR and gene targeting in Aspergillus nidulans. Nat. Protoc. 1: 3111-3120. http://dx.doi.org/10.1038/nprot.2006.405.
43. Peñalva MA. 2005. Tracing the endocytic pathway of Aspergillus nidulans with FM4-64. Fungal Genet. Biol. 42: 963-975. http://dx.doi.org/10.1016/j.fgb.2005.09.004.
44. Reichard U, Monod M, Odds F, Ruchel R. 1997. Virulence of an aspergillopepsin-deficient mutant of Aspergillus fumigatus and evidence for another aspartic proteinase linked to the fungal cell wall. J. Med. Vet. Mycol. 35: 189-196. http://dx.doi.org/10.1080/02681219780001131.
45. Cramer RA, Gamcsik MP, Brooking RM, Najvar LK, Kirkpatrick WR, Patterson TF, Balibar CJ, Graybill JR, Perfect JR, Abraham SN, Steinbach WJ. 2006. Disruption of a nonribosomal peptide synthetase in Aspergillus fumigatus eliminates gliotoxin production. Eukaryot. Cell 5: 972-980. http://dx.doi.org/10.1128/EC.00049-06.
46. Weber K, Bolander M, Sarkar G. 1998. PIG-B: a homemade monophasic cocktail for the extraction of RNA. Mol. Biotechnol. 9: 73-77. http://dx.doi.org/10.1007/BF02752699.
47. Fuchs B, O'Brien E, Khoury J, Mylonakis E. 2010. Methods for using Galleria mellonella as a model host to study fungal pathogenesis. Virulence 1: 475-482. http://dx.doi.org/10.4161/viru.1.6.12985.
48. Adams TH, Boylan MT, Timberlake WE. 1988. brlA is necessary and sufficient to direct conidiophore development in Aspergillus nidulans. Cell 54: 353-362. http://dx.doi.org/10.1016/0092-8674(88)90198-5.
49. Richie DL, Hartl L, Aimanianda V, Winters MS, Fuller KK, Miley MD, White S, McCarthy JW, Latge PJ, Feldmesser M, Rhodes JC, Askew DS. 2009. A role for the unfolded protein response (upr) in virulence and antifungal susceptibility in Aspergillus fumigatus. PLoS Pathog. 5: e1000258. http://dx.doi.org/10.1371/journal.ppat.1000258.
50. Gardiner D, Howlett BJ. 2005. Bioinformatic and expression analysis of the putative gliotoxin biosynthetic gene cluster of Aspergillus fumigatus. FEMS Microbiol. Lett. 248: 241-248. http://dx.doi.org/10.1016/j.femsle.2005.05.046.
51. Kupfahl C, Heinekamp T, Geginat G, Ruppert T, Hartl A, Hof H, Brakhage AA. 2006. Deletion of the gliP gene of Aspergillus fumigatus results in loss of gliotoxin production but has no effect on virulence of the fungus in a low-dose mouse infection model. Mol. Microbiol. 62: 292-302. http://dx.doi.org/10.1111/j.1365-2958.2006.05373.x.
52. Spikes S, Xu R, Nguyen CK, Chamilos G, Kontoyiannis DP, Jacobson RH, Ejzykowicz DE, Chiang LY, Filler SG, May GS. 2008. Gliotoxin production in Aspergillus fumigatus contributes to host-specific differences in virulence. J. Infect. Dis. 197: 479-486. http://dx.doi.org/10.1086/525044.
53. Sugui JA, Pardo J, Chang YC, Zarember KA, Nardone G, Galvez EM, Mullbacher A, Gallin JI, Simon MM, Kwon-Chung KJ. 2007. Gliotoxin is a virulence factor of Aspergillus fumigatus: gliP deletion attenuates virulence in mice immunosuppressed with hydrocortisone. Eukaryot. Cell 6: 1562-1569. http://dx.doi.org/10.1128/EC.00141-07.
54. Reeves EP, Messina CG, Doyle S, Kavanagh K. 2004. Correlation between gliotoxin production and virulence of Aspergillus fumigatus in Galleria mellonella. Mycopathologia 158: 73-79. http://dx.doi.org/10.1023/B:MYCO.0000038434.55764.16.
55. Mylonakis E, Moreno R, El Khoury JB, Idnurm A, Heitman J, Calderwood SB, Ausubel FM, Diener A. 2005. Galleria mellonella as a model system to study Cryptococcus neoformans pathogenesis. Infect. Immun. 73: 3842-3850. http://dx.doi.org/10.1128/IAI.73.7.3842-3850.2005.
56. Mylonakis E. 2008. Galleria mellonella and the study of fungal pathogenesis: making the case for another genetically tractable model host. Mycopathologia 165: 1-3. http://dx.doi.org/10.1007/s11046-007-9082-z.
57. Dunphy GB, Oberholzer U, Whiteway M, Zakarian RJ, Boomer I. 2003. Virulence of Candida albicans mutants toward larval Galleria mellonella (Insecta, Lepidoptera, Galleridae). Can. J. Microbiol. 49: 514-524. http://dx.doi.org/10.1139/w03-064.
58. Brennan M, Thomas DY, Whiteway M, Kavanagh K. 2002. Correlation between virulence of Candida albicans mutants in mice and Galleria mellonella larvae. FEMS Immunol. Med. Microbiol. 34: 153-157. http://dx.doi.org/10.1111/j.1574-695X.2002.tb00617.x.
59. Jackson JC, Higgins LA, Lin X. 2009. Conidiation color mutants of Aspergillus fumigatus are highly pathogenic to the heterologous insect host Galleria mellonella. PLoS One 4: e4224. http://dx.doi.org/10.1371/journal.pone.0004224.
60. Kavanagh K, Reeves EP. 2004. Exploiting the potential of insects for in vivo pathogenicity testing of microbial pathogens. FEMS Microbiol. Rev. 28: 101-112. http://dx.doi.org/10.1016/j.femsre.2003.09.002.
61. Ratcliffe NA. 1985. Invertebrate immunity-a primer for the nonspecialist. Immunol. Lett. 10: 253-270. http://dx.doi.org/10.1016/0165-2478(85)90100-2.
62. Tojo S, Naganuma F, Arakawa K, Yokoo S. 2000. Involvement of both granular cells and plasmatocytes in phagocytic reactions in the greater wax moth, Galleria mellonella. J. Insect. Physiol. 46: 1129-1135. http://dx.doi.org/10.1016/S0022-1910(99)00223-1.
63. Samson RA. 1999. The genus Aspergillus with special regard to the Aspergillus fumigatus group. Contrib. Microbiol. 2: 5-20. http://dx.doi.org/10.1159/000060298.
64. Han S, Adams TH. 2001. Complex control of the developmental regulatory locus brlA in Aspergillus nidulans. Mol. Genet. Genomics 266: 260-270. http://dx.doi.org/10.1007/s004380100552.
65. Marshall MA, Timberlake WE. 1991. Aspergillus nidulans wetA activates spore-specific gene expression. Mol. Cell. Biol. 11: 56-62.
66. Choi HS, Shim JS, Kim JA, Kang SW, Kwon HJ. 2007. Discovery of gliotoxin as a new small molecule targeting thioredoxin redox system. Biochem. Biophys. Res. Commun. 359: 523-528. http://dx.doi.org/10.1016/j.bbrc.2007.05.139.
67. Scharf DH, Heinekamp T, Remme N, Hortschansky P, Brakhage AA, Hertweck C. 2012. Biosynthesis and function of gliotoxin in Aspergillus fumigatus. Appl. Microbiol. Biotechnol. 93: 467-472. http://dx.doi.org/10.1007/s00253-011-3689-1.
68. Kolattukudy PE, Lee JD, Rogers LM, Zimmerman P, Ceselski S, Fox B, Stein B, Copelan EA. 1993. Evidence for possible involvement of an elastolytic serine-protease in aspergillosis. Infect. Immun. 61: 2357-2368.
69. Duran RM, Gregersen S, Smith TD, Bhetariya PJ, Cary JW, Harris-Coward PY, Mattison CP, Grimm C, Calvo AM. 4 March 2014. The role of Aspergillus flavus veA in the production of extracellular proteins during growth on starch substrates. Appl. Microbiol. Biotechnol. http://dx.doi.org/10.1007/s00253-014-5598-6.
70. Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T) method. Methods 24: 402-408. http://dx.doi.org/10.1006/meth.2001.1262.