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

  • Applied genetics and molecular biotechnology
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Abstract

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.

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Acknowledgments

We thank Carmen Schult and Eva-Maria Neumann for excellent technical assistance, Andrea Perner for HRMS measurements, and Franziska Schmidt for macrophage cultivations. We also thank Thorsten Heinekamp and Maria Straßburger for insightful conversations. This work was supported by the Deutsche Forschungsgemeinschaft (DFG)-funded Graduate School of Excellence, Jena School for Microbial Communication, and the DFG-funded collaborative research center / Transregio (SFB/TR) 124 Human-pathogenic fungi and their human host–networks of interaction FungiNet (project A1 to AB and project B4 to MTF).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany

    Derek J. Mattern, Hanno Schoeler, Jakob Weber, Silvia Novohradská, Falk Hillmann & Axel A. Brakhage

  2. Friedrich Schiller University Jena, Jena, Germany

    Derek J. Mattern, Hanno Schoeler, Jakob Weber, Silvia Novohradská, Kaswara Kraibooj, Marc Thilo Figge & Axel A. Brakhage

  3. Department of Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany

    Kaswara Kraibooj & Marc Thilo Figge

  4. Department of Infection Biology, Leibniz Institute for Infection Biology and Natural Product Research (HKI), Jena, Germany

    Hans-Martin Dahse

  5. Leibniz Junior Research Group - Biobricks of Microbial Natural Product Syntheses, Jena, Germany

    Vito Valiante

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  1. Derek J. Mattern
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  2. Hanno Schoeler
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Correspondence to Axel A. Brakhage.

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Mattern, D.J., Schoeler, H., Weber, J. et al. Identification of the antiphagocytic trypacidin gene cluster in the human-pathogenic fungus Aspergillus fumigatus . Appl Microbiol Biotechnol 99, 10151–10161 (2015). https://doi.org/10.1007/s00253-015-6898-1

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