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  3. Aspergillus fumigatus hijacks human p11 to redirect fungal-containing phagosomes to non-degradative pathway

Aspergillus fumigatus hijacks human p11 to redirect fungal-containing phagosomes to non-degradative pathway

  • Cell Host Microbe. 2023 Mar 8;31(3):373-388.e10. doi: 10.1016/j.chom.2023.02.002.
Lei-Jie Jia 1,  Muhammad Rafiq 2,  Lukáš Radosa 1,  Peter Hortschansky 1,  Cristina Cunha 3,  Zoltán Cseresnyés 4,  Thomas Krüger 1,  Franziska Schmidt 1,  Thorsten Heinekamp 1,  Maria Straßburger 5,  Bettina Löffler 6,  Torsten Doenst 7,  João F Lacerda 8,  António Campos Jr 9,  Marc Thilo Figge 10,  Agostinho Carvalho 3,  Olaf Kniemeyer 1,  Axel A Brakhage 11
Affiliations

Affiliations

  • 1 Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745 Jena, Germany.
  • 2 Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745 Jena, Germany; Institute of Microbiology, Friedrich Schiller University, 07745 Jena, Germany.
  • 3 Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
  • 4 Research Group Applied Systems Biology, Leibniz-HKI, Jena, Germany.
  • 5 Transfer Group Anti-infectives, Leibniz-HKI, 07745 Jena, Germany.
  • 6 Institute of Medical Microbiology, Jena University Hospital, 07747 Jena, Germany.
  • 7 Klinik für Herz- und Thoraxchirurgie, Jena University Hospital, 07747 Jena, Germany.
  • 8 Serviço de Hematologia e Transplantação de Medula, Hospital de Santa Maria, 1649-035 Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.
  • 9 Serviço de Transplantação de Medula Óssea, Instituto Português de Oncologia do Porto, 4200-072 Porto, Portugal.
  • 10 Institute of Microbiology, Friedrich Schiller University, 07745 Jena, Germany; Research Group Applied Systems Biology, Leibniz-HKI, Jena, Germany.
  • 11 Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745 Jena, Germany; Institute of Microbiology, Friedrich Schiller University, 07745 Jena, Germany. Electronic address: axel.brakhage@leibniz-hki.de.
PMID: 36893734 DOI: 10.1016/j.chom.2023.02.002
Abstract

The decision whether endosomes enter the degradative or recycling pathway in mammalian cells is of fundamental importance for pathogen killing, and its malfunctioning has pathological consequences. We discovered that human p11 is a critical factor for this decision. The HscA protein present on the conidial surface of the human-pathogenic fungus Aspergillus fumigatus anchors p11 on conidia-containing phagosomes (PSs), excludes the PS maturation mediator Rab7, and triggers binding of exocytosis mediators Rab11 and Sec15. This reprogramming redirects PSs to the non-degradative pathway, allowing A. fumigatus to escape cells by outgrowth and expulsion as well as transfer of conidia between cells. The clinical relevance is supported by the identification of a single nucleotide polymorphism in the non-coding region of the S100A10 (p11) gene that affects mRNA and protein expression in response to A. fumigatus and is associated with protection against invasive pulmonary aspergillosis. These findings reveal the role of p11 in mediating Fungal PS evasion.

Keywords

Aspergillus fumigatus; Rab11; Rab7; annexin A2; exocytosis; heat shock protein; human p11; invasive aspergillosis; phagosome maturation; recycling endosome.

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