Identification of the antiphagocytic trypacidin gene cluster in the human-pathogenic fungus Aspergillus fumigatus

Applied Microbiology and Biotechnology

Volumn 99, Issue 23, 2015, Pages 10151-10161

  Mattern, Derek J ^a,b   Schoeler, Hanno ^a,b   Weber, Jakob ^a,b   Novohradská, Silvia ^a,b   Kraibooj, Kaswara ^a,b   Dahse, Hans Martin ^a   Hillmann, Falk ^a   Valiante, Vito ^c   Figge, Marc Thilo ^a,b   Brakhage, Axel A ^a,b  

^a HANS KNÖLL INSTITUTE   (Germany)

^b FRIEDRICH SCHILLER UNIVERSITY JENA   (Germany)

^c Leibniz Junior Research Group Biobricks of Microbial Natural Product Syntheses   (Germany)

Author keywords

Aspergillus fumigatus; Dictyostelium discoideum; Genome mining; Macrophage; Polyketide; Trypacidin

Indexed keywords

ANTIGEN-ANTIBODY REACTIONS; ASPERGILLUS; BIOCHEMISTRY; BIOSYNTHESIS; ENCODING (SYMBOLS); ENZYMES; FUNGI; GENE ENCODING; KETONES; MACROPHAGES; METABOLITES; PLANTS (BOTANY); PROTOZOA;

ASPERGILLUS FUMIGATUS; DICTYOSTELIUM DISCOIDEUM; GENOME MINING; POLYKETIDES; TRYPACIDIN;

GENES;

ANTIAMEBIC AGENT; ENDOCROCIN; FUMICYCLINE; TRYPACIDIN; UNCLASSIFIED DRUG; BIOLOGICAL PRODUCT; IMMUNOLOGIC FACTOR;

ANTIMICROBIAL ACTIVITY; BIOTECHNOLOGY; CELLS AND CELL COMPONENTS; ENZYME ACTIVITY; EUKARYOTE; FUNGUS; GENE EXPRESSION; GENOME; IDENTIFICATION METHOD; METABOLITE; PATHOGEN; PROTOZOAN; TOXIN;

ANIMAL CELL; ARTICLE; ASPERGILLUS FUMIGATUS; CELL PROTECTION; CONIDIUM; CONTROLLED STUDY; DELETION MUTANT; DICTYOSTELIUM DISCOIDEUM; DRUG SENSITIVITY; ENZYME SYNTHESIS; FUNGAL GENE; FUNGAL STRAIN; FUNGUS IDENTIFICATION; FUNGUS MUTANT; GENE CLUSTER; GENE DELETION; GENETIC CODE; MACROPHAGE; MOUSE; NONHUMAN; PHAGOCYTOSIS; WILD TYPE; ANIMAL; CELL CULTURE; DICTYOSTELIUM; DRUG EFFECTS; GENETIC COMPLEMENTATION; GENETICS; IMMUNOLOGY; LUNG ALVEOLUS MACROPHAGE; METABOLISM; MICROBIOLOGY; MULTIGENE FAMILY; PHYSIOLOGY;

ASPERGILLUS FUMIGATUS; DICTYOSTELIUM DISCOIDEUM; FUNGI;

ANIMALS; ASPERGILLUS FUMIGATUS; BIOLOGICAL PRODUCTS; CELLS, CULTURED; DICTYOSTELIUM; GENE DELETION; GENETIC COMPLEMENTATION TEST; IMMUNOLOGIC FACTORS; MACROPHAGES, ALVEOLAR; MICE; MULTIGENE FAMILY; PHAGOCYTOSIS;

EID: 84947023643     PISSN: 01757598     EISSN: 14320614     Source Type: Journal    
DOI: 10.1007/s00253-015-6898-1     Document Type: Article

References (54)

1. Aimanianda V, Bayry J, Bozza S, Kniemeyer O, Perruccio K, Elluru SR, Clavaud C, Paris S, Brakhage AA, Kaveri SV, Romani L, Latgé JP (2009) Surface hydrophobin prevents immune recognition of airborne fungal spores. Nature 460(7259):1117–1121
2. Balan J, Ebringer L, Nemec P (1964) Trypacidin a new antiprotozoal antibiotic. Naturwissenschaften 51(9):227
3. Balan J, Ebringer L, Nemec P, Kovac S, Dobias J (1963) Antiprotozoal antibiotics. II. Isolation and characterization of trypacidin, a new antibiotic, active against Trypanosoma cruzi and Toxoplasma gondii. J Antibiot (Tokyo) 6:157–160
4. Baldin C, Valiante V, Krüger T, Schafferer L, Haas H, Kniemeyer O, Brakhage AA (2015) Comparative proteomics of a tor inducible Aspergillus fumigatus mutant reveals involvement of the Tor kinase in iron regulation. Proteomics 15(13):2230–2243
5. Brakhage AA (2013) Regulation of fungal secondary metabolism. Nat Rev Microbiol 11(1):21–32
6. Brakhage AA, Langfelder K (2002) Menacing mold: the molecular biology of Aspergillus fumigatus. Annu Rev Microbiol 56:433–455
7. Brakhage AA (2005) Systemic fungal infections caused by Aspergillus species: epidemiology, infection process and virulence determinants. Curr Drug Targets 6(8):875–886
8. Bergmann S, Schümann J, Scherlach K, Lange C, Brakhage AA, Hertweck C (2007) Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans. Nat Chem Biol 3(4):213–217
9. Berthier E, Lim FY, Deng Q, Guo CJ, Kontoyiannis DP, Wang CC, Rindy J, Beebe DJ, Huttenlocher A, Keller NP (2013) Low-volume toolbox for the discovery of immunosuppressive fungal secondary metabolites. PLoS Pathog 9(4): e1003289
10. Cerqueira GC, Arnaud MB, Inglis DO, Skrzypek MS, Binkley G, Simison M, Miyasato SR, Binkley J, Orvis J, Shah P, Wymore F, Sherlock G, Wortman JR (2013) The Aspergillus genome database (AspGD): multispecies curation and incorporation of RNA-Seq data to improve structural gene annotations. Nucl Acids Res 42(Database issue):D705–D710
11. Chai LY, Vonk AG, Kullberg BJ, Verweij PE, Verschueren I, van der Meer JW, Joosten LA, Latgé JP, Netea MG (2011) Aspergillus fumigatus cell wall components differentially modulate host TLR2 and TLR4 responses. Microbes Infect 13(2):151–159
12. Chiang YM, Szewczyk E, Davidson AD, Entwistle R, Keller NP, Wang CC, Oakley BR (2010) Characterization of the Aspergillus nidulans monodictyphenone gene cluster. Appl Environ Microbiol 76(7):2067–2074
13. Chooi YH, Fang J, Liu H, Filler SG, Wang P, Tang Y (2013) Genome mining of a prenylated and immunosuppressive polyketide from pathogenic fungi. Org Lett 15(4):780–783
14. Coyle CM, Panaccione DG (2005) An ergot alkaloid biosynthesis gene and clustered hypothetical genes from Aspergillus fumigatus. Appl Environ Microbiol 71(6):3112–3118
15. Ebringer L, Catar G, Balan J, Nemec P, Kov’ac S (1963) Antiprotozoal antibiotics. III Preliminary Report on the Effect of Trypacidin on Experimental Toxoplasmosis J Antibiot (Tokyo) 16:161–162
16. Ebringer L, Balan J, Nemec P (1964) Incidence of antiprotozoal substances in Aspergillaceae. J Protozool 11(2):153–156
17. Fischer G, Müller T, Ostrowski R, Dott W (1999) Mycotoxins of Aspergillus fumigatus in pure culture and in native bioaerosols from compost facilities. Chemosphere 38(8):1745–1755
18. Frisvad JC, Rank C, Nielsen KF, Larsen TO (2009) Metabolomics of Aspergillus fumigatus. Med Mycol 47(Suppl 1):S72–S79
19. Gauthier T, Wang X, Sifuentes Dos Santos J, Fysikopoulos A, Tadrist S, Canlet C, Artigot MP, Loiseau N, Oswald IP, Puel O (2012) Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cells. PLoS One 7(2):e29906
20. Gibson DG, Young L, Chuang RY, Venter JC, Hutchison III CA, Smith HO (2009) Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Methods 6(5):343–345
21. Guo CJ, Wang CC (2014) Recent advances in genome mining of secondary metabolites in Aspergillus terreus. Front Microbiol 23(717):1–13
22. Heinekamp T, Schmidt H, Lapp K, Pähtz V, Shopova I, Köster-Eiserfunke N, Krüger T, Kniemeyer O, Brakhage AA (2015) Interference of Aspergillus fumigatus with the immune response. Semin Immunpathol 37(2):141–152
23. Hillmann F, Novohradská S, Mattern DJ, Forberger T, Heinekamp T, Westermann M, Winckler T, Brakhage AA (2015) Virulence determinants of the human pathogenic fungus Aspergillus fumigatus protect against soil amoeba predation. Environ Microbiol doi:. doi:10.1111/1462-2920.12808
24. Ibrahim-Granet O, Philippe B, Boleti H, Boisvieux-Ulrich E, Grenet D, Stern M, Latgé JP (2003) Phagocytosis and intracellular fate of Aspergillus fumigatus conidia in alveolar macrophages. Infect Immun 71(2):891–903
25. Jahn B, Koch A, Schmidt A, Wanner G, Gehringer H, Bhakdi S, Brakhage AA (1997) Isolation and characterization of a pigmentless-conidium mutant of Aspergillus fumigatus with altered conidial surface and reduced virulence. Infect Immun 65(12):5110–5117
26. Kraibooj K, Park HR, Dahse HM, Skerka C, Voigt K, Figge MT (2014) Virulent strain of Lichtheimia corymbifera shows increased phagocytosis by macrophages as revealed by automated microscopy image analysis. Mycoses Suppl 3:56–66
27. König CC, Scherlach K, Schroeckh V, Horn F, Nietzsche S, Brakhage AA, Hertweck C (2013) Bacterium induces cryptic meroterpenoid pathway in the pathogenic fungus Aspergillus fumigatus. Chembiochem 14(8):938–942
28. Kurup VP (1984) Interaction of Aspergillus fumigatus spores and pulmonary alveolar macrophages of rabbits. Immunobiology 166(1):53–61
29. Lim FY, Hou Y, Chen Y, Oh JH, Lee I, Bugni TS, Keller NP (2012) Genome based cluster deletion reveals an endocrocin biosynthetic pathway in Aspergillus fumigatus. Appl Environ Microbiol 78(12):4117–4125
30. Luther K, Torosantucci A, Brakhage AA, Heesemann J, Ebel F (2007) Phagocytosis of Aspergillus fumigatus conidia by murine macrophages involves recognition by the dectin-1 β-glucan receptor and toll-like receptor 2. Cell Microbiol 9(2):368–381
31. Maerker C, Rohde M, Brakhage AA, Brock M (2005) Methylcitrate synthase from Aspergillus fumigatus. Propionyl-CoA affects polyketide synthesis, growth and morphology of conidia. FEBS J 272(14):3615–3630
32. Marchler-Bauer A, Panchenko AR, Shoemaker BA, Thiessen PA, Geer LY, Bryant SH (2002) CDD: a database of conserved domain alignments with links to domain three-dimensional structure. Nucl Acids Res 30(1):281–283
33. Mech F, Thywissen A, Guthke R, Brakhage AA, Figge MT (2011) Automated image analysis of the host-pathogen interaction between phagocytes and Aspergillus fumigatus. PLoS One 6(5):e19591
34. Mech F, Wilson D, Lehnert T, Hube B, Figge MT (2014) Epithelial invasion outcompetes hypha development during Candida albicans infection as revealed by an image-based systems biology approach. Cytometry A 85(2):126–139
35. Meier A, Kirschning CJ, Nikolaus T, Wagner H, Heesemann J, Ebel F (2003) Toll-like receptor (TLR) 2 and TLR4 are essential for Aspergillus-induced activation of murine macrophages. Cell Microbiol 5(8):561–570
36. Nemec P, Balan J, Ebringer L (1963) Antiprotozoal antibiotics. I J Antibiot (Tokyo) 16:155–156
37. Netea MG, Warris A, Van der Meer JW, Fenton MJ, Verver-Janssen TJ, Jacobs LE, Andresen T, Verweij PE, Kullberg BJ (2003) Aspergillus fumigatus evades immune recognition during germination through loss of toll-like receptor-4-mediated signal transduction. J Infect Dis 188(2):320–326
38. Nielsen ML, Nielsen JB, Rank C, Klejnstrup ML, Holm DK, Brogaard KH, Hansen BG, Frisvad JC, Larsen TO, Mortensen UH (2011) A genome-wide polyketide synthase deletion library uncovers novel genetic links to polyketides and meroterpenoids in Aspergillus nidulans. F E M S Microbiol Lett 321(2):157–166
39. Nielsen MT, Nielsen JB, Anyaogu DC, Holm DK, Nielsen KF, Larsen TO, Mortensen UH (2013) Heterologous reconstitution of the intact geodin gene cluster in Aspergillus nidulans through a simple and versatile PCR based approach. PLoS One 8(8):e72871
40. Parker GF, Jenner PC (1968) Distribution of trypacidin in cultures of Aspergillus fumigatus. Appl Microbiol 16(8):1251–1252
41. Philippe B, Ibrahim-Granet O, Prévost MC, Gougerot-Pocidalo MA, Sanchez Perez M, Van der Meeren A, Latgé JP (2003) Killing of Aspergillus fumigatus by alveolar macrophages is mediated by reactive oxidant intermediates. Infect Immun 71(6):3034–3042
42. 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(2):467–472
43. Scharf DH, Heinekamp T, Brakhage AA (2014a) Human and plant fungal pathogens: the role of secondary metabolites. PLoS Pathog 10(1):e1003859
44. Scharf DH, Habel A, Heinekamp T, Brakhage AA, Hertweck C (2014b) Opposed effects of enzymatic gliotoxin N- and S-methylations. J Am Chem Soc 136(33):11674–11679
45. Steele C, Rapaka RR, Metz A, Pop SM, Williams DL, Gordon S, Kolls JK, Brown GD (2005) The β-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus. PLoS Pathog 1(4):e42
46. 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(6):3111–3120
47. Szewczyk E, Chiang YM, Oakley CE, Davidson AD, Wang CCC, Oakley BR (2008) Identification and characterization of the asperthecin gene cluster of Aspergillus nidulans. Appl Environ Microbiol 74(24):7607–7612
48. Tae H, Sohng JK, Park K (2009) MapsiDB: an integrated web database for type I polyketide synthases. Bioprocess Biosyst Eng 32(6):723–727
49. Then Bergh KT, Litzka O, Brakhage AA (1996) Identification of a major cis-acting DNA element controlling the bidirectionally transcribed penicillin biosynthesis genes acvA (pcbAB) and ipnA (pcbC) of Aspergillus nidulans. J Bacteriol 178(13):3908–3916
50. Thywißen A, Heinekamp T, Dahse HM, Schmaler-Ripcke J, Nietzsche S, Zipfel PF, Brakhage AA (2011) Conidial dihydroxynaphthalene melanin of the human pathogenic fungus Aspergillus fumigatus interferes with the host endocytosis pathway. Front Microbiol 2:96
51. Turner WB (1965) The production of trypacidin and monomethylsulochrin by Aspergillus fumigatus. J Chem Soc 6658-6659
52. Unkles SE, Valiante V, Mattern DJ, Brakhage AA (2014) Synthetic biology tools for bioprospecting of natural products in eukaryotes. Chem Biol 21(4):502–508
53. Van Waeyenberghe L, Baré J, Pasmans F, Claeys M, Bert W, Haesebrouck F, Houf K, Martel A (2013) Interaction of Aspergillus fumigatus conidia with Acanthamoeba castellanii parallels macrophage-fungus interactions. Environ Microbiol Rep 5(6):819–824
54. Yaegashi J, Oakley BR, Wang CC (2014) Recent advances in genome mining of secondary metabolite biosynthetic gene clusters and the development of heterologous expression systems in Aspergillus nidulans. J Ind Microbiol Biotechnol 41(2):433–442