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

Verfasser / Beitragende:
[Derek Mattern, Hanno Schoeler, Jakob Weber, Silvia Novohradská, Kaswara Kraibooj, Hans-Martin Dahse, Falk Hillmann, Vito Valiante, Marc Figge, Axel Brakhage]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/23(2015-12-01), 10151-10161
Format:
Artikel (online)
ID: 605504679
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024 7 0 |a 10.1007/s00253-015-6898-1  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00253-015-6898-1 
245 0 0 |a Identification of the antiphagocytic trypacidin gene cluster in the human-pathogenic fungus Aspergillus fumigatus  |h [Elektronische Daten]  |c [Derek Mattern, Hanno Schoeler, Jakob Weber, Silvia Novohradská, Kaswara Kraibooj, Hans-Martin Dahse, Falk Hillmann, Vito Valiante, Marc Figge, Axel Brakhage] 
520 3 |a The opportunistic human pathogen Aspergillus fumigatus produces numerous different natural products. The genetic basis for the biosynthesis of a number of known metabolites has remained unknown. The gene cluster encoding for the biosynthesis of the conidia-bound metabolite trypacidin is of particular interest because of its antiprotozoal activity and possible role in the infection process. Here, we show that the genes encoding the biosynthesis enzymes of trypacidin reside within an orphan gene cluster in A. fumigatus. Genome mining identified tynC as an uncharacterized polyketide synthase with high similarity to known enzymes, whose products are structurally related to trypacidin including endocrocin and fumicycline. Gene deletion of tynC resulted in the complete absence of trypacidin production, which was fully restored when the mutant strain was complemented with the wild-type gene. When confronted with macrophages, the tynC deletion mutant conidia were more frequently phagocytosed than those of the parental wild-type strain. This was also found for phagocytic amoebae of the species Dictyostelium discoideum, which showed increased phagocytosis of ΔtynC conidia. Both macrophages and amoebae were also sensitive to trypacidin. Therefore, our results suggest that the conidium-bound trypacidin could have a protective function against phagocytes both in the environment and during the infection process. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a Aspergillus fumigatus  |2 nationallicence 
690 7 |a Genome mining  |2 nationallicence 
690 7 |a Trypacidin  |2 nationallicence 
690 7 |a Polyketide  |2 nationallicence 
690 7 |a Macrophage  |2 nationallicence 
690 7 |a Dictyostelium discoideum  |2 nationallicence 
700 1 |a Mattern  |D Derek  |u Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany  |4 aut 
700 1 |a Schoeler  |D Hanno  |u Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany  |4 aut 
700 1 |a Weber  |D Jakob  |u Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany  |4 aut 
700 1 |a Novohradská  |D Silvia  |u Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany  |4 aut 
700 1 |a Kraibooj  |D Kaswara  |u Friedrich Schiller University Jena, Jena, Germany  |4 aut 
700 1 |a Dahse  |D Hans-Martin  |u Department of Infection Biology, Leibniz Institute for Infection Biology and Natural Product Research (HKI), Jena, Germany  |4 aut 
700 1 |a Hillmann  |D Falk  |u Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany  |4 aut 
700 1 |a Valiante  |D Vito  |u Leibniz Junior Research Group - Biobricks of Microbial Natural Product Syntheses, Jena, Germany  |4 aut 
700 1 |a Figge  |D Marc  |u Friedrich Schiller University Jena, Jena, Germany  |4 aut 
700 1 |a Brakhage  |D Axel  |u Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/23(2015-12-01), 10151-10161  |x 0175-7598  |q 99:23<10151  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-015-6898-1  |q text/html  |z Onlinezugriff via DOI 
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900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-015-6898-1  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Mattern  |D Derek  |u Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Schoeler  |D Hanno  |u Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Weber  |D Jakob  |u Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Novohradská  |D Silvia  |u Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kraibooj  |D Kaswara  |u Friedrich Schiller University Jena, Jena, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Dahse  |D Hans-Martin  |u Department of Infection Biology, Leibniz Institute for Infection Biology and Natural Product Research (HKI), Jena, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Hillmann  |D Falk  |u Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Valiante  |D Vito  |u Leibniz Junior Research Group - Biobricks of Microbial Natural Product Syntheses, Jena, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Figge  |D Marc  |u Friedrich Schiller University Jena, Jena, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Brakhage  |D Axel  |u Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/23(2015-12-01), 10151-10161  |x 0175-7598  |q 99:23<10151  |1 2015  |2 99  |o 253