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

作者: Derek J. Mattern , Hanno Schoeler , Jakob Weber , Silvia Novohradská , Kaswara Kraibooj

DOI: 10.1007/S00253-015-6898-1

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摘要: The opportunistic human pathogen Aspergillus fumigatus produces numerous different natural products. genetic basis for the biosynthesis of a number known metabolites has remained unknown. gene cluster encoding conidia-bound metabolite trypacidin is particular interest because its antiprotozoal activity and possible role in infection process. Here, we show that genes enzymes reside within an orphan A. fumigatus. Genome mining identified tynC as uncharacterized polyketide synthase with high similarity to enzymes, whose products are structurally related including endocrocin fumicycline. Gene deletion resulted complete absence production, which was fully restored when mutant strain complemented wild-type gene. When confronted macrophages, conidia were more frequently phagocytosed than those parental strain. This also found phagocytic amoebae species Dictyostelium discoideum, showed increased phagocytosis ΔtynC conidia. Both macrophages sensitive trypacidin. Therefore, our results suggest conidium-bound could have protective function against phagocytes both environment during

参考文章(54)
Catar G, Nemec P, Ebringer L, Kov'ac S, Balan J, ANTIPROTOZOAL ANTIBIOTICS. III. PRELIMINARY REPORT ON THE EFFECT OF TRYPACIDIN ON EXPERIMENTAL TOXOPLASMOSIS. The Journal of Antibiotics. ,vol. 16, pp. 161- ,(1963)
Nemec P, Ebringer L, Kovac S, Dobias J, Balan J, ANTIPROTOZOAL ANTIBIOTICS. II. ISOLATION AND CHARACTERIZATION OF TRYPACIDIN, A NEW ANTIBIOTIC, ACTIVE AGAINST TRYPANOSOMA CRUZI AND TOXOPLASMA GONDII. The Journal of Antibiotics. ,vol. 16, pp. 157- ,(1963)
Franziska Mech, Duncan Wilson, Teresa Lehnert, Bernhard Hube, Marc Thilo Figge, Epithelial invasion outcompetes hypha development during Candida albicans infection as revealed by an image-based systems biology approach. Cytometry Part A. ,vol. 85, pp. 126- 139 ,(2014) , 10.1002/CYTO.A.22418
Michael L. Nielsen, Jakob B. Nielsen, Christian Rank, Marie L. Klejnstrup, Dorte K. Holm, Katrine H. Brogaard, Bjarne G. Hansen, Jens C. Frisvad, Thomas O. Larsen, Uffe H. Mortensen, A genome-wide polyketide synthase deletion library uncovers novel genetic links to polyketides and meroterpenoids in Aspergillus nidulans. Fems Microbiology Letters. ,vol. 321, pp. 157- 166 ,(2011) , 10.1111/J.1574-6968.2011.02327.X
G F Parker, P C Jenner, Distribution of trypacidin in cultures of Aspergillus fumigatus. Applied and Environmental Microbiology. ,vol. 16, pp. 1251- 1252 ,(1968) , 10.1128/AM.16.8.1251-1252.1968
Claudia Maerker, Manfred Rohde, Axel A. Brakhage, Matthias Brock, Methylcitrate synthase from Aspergillus fumigatus. Propionyl-CoA affects polyketide synthesis, growth and morphology of conidia. FEBS Journal. ,vol. 272, pp. 3615- 3630 ,(2005) , 10.1111/J.1742-4658.2005.04784.X
Falk Hillmann, Silvia Novohradská, Derek J. Mattern, Tilmann Forberger, Thorsten Heinekamp, Martin Westermann, Thomas Winckler, Axel A. Brakhage, Virulence determinants of the human pathogenic fungusAspergillus fumigatusprotect against soil amoeba predation Environmental Microbiology. ,vol. 17, pp. 2858- 2869 ,(2015) , 10.1111/1462-2920.12808
Sebastian Bergmann, Julia Schümann, Kirstin Scherlach, Corinna Lange, Axel A Brakhage, Christian Hertweck, Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans Nature Chemical Biology. ,vol. 3, pp. 213- 217 ,(2007) , 10.1038/NCHEMBIO869
Daniel G Gibson, Lei Young, Ray-Yuan Chuang, J Craig Venter, Clyde A Hutchison, Hamilton O Smith, Enzymatic assembly of DNA molecules up to several hundred kilobases Nature Methods. ,vol. 6, pp. 343- 345 ,(2009) , 10.1038/NMETH.1318
Christine M. Coyle, Daniel G. Panaccione, An Ergot Alkaloid Biosynthesis Gene and Clustered Hypothetical Genes from Aspergillus fumigatus Applied and Environmental Microbiology. ,vol. 71, pp. 3112- 3118 ,(2005) , 10.1128/AEM.71.6.3112-3118.2005