Enolase From Aspergillus fumigatus Is a Moonlighting Protein That Binds the Human Plasma Complement Proteins Factor H, FHL-1, C4BP, and Plasminogen
The opportunistic fungal pathogen Aspergillus fumigatus can cause severe infections, particularly in immunocompromised individuals. Upon infection, A. fumigatus faces the powerful and directly acting immune defense of the human host. The mechanisms on how A. fumigatus evades innate immune attack and...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02573/full |
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| author | Prasad Dasari Naile Koleci Iordana A. Shopova Dirk Wartenberg Niklas Beyersdorf Stefanie Dietrich Alfredo Sahagún-Ruiz Marc Thilo Figge Marc Thilo Figge Christine Skerka Axel A. Brakhage Axel A. Brakhage Peter F. Zipfel Peter F. Zipfel |
| author_facet | Prasad Dasari Naile Koleci Iordana A. Shopova Dirk Wartenberg Niklas Beyersdorf Stefanie Dietrich Alfredo Sahagún-Ruiz Marc Thilo Figge Marc Thilo Figge Christine Skerka Axel A. Brakhage Axel A. Brakhage Peter F. Zipfel Peter F. Zipfel |
| author_sort | Prasad Dasari |
| collection | DOAJ |
| description | The opportunistic fungal pathogen Aspergillus fumigatus can cause severe infections, particularly in immunocompromised individuals. Upon infection, A. fumigatus faces the powerful and directly acting immune defense of the human host. The mechanisms on how A. fumigatus evades innate immune attack and complement are still poorly understood. Here, we identify A. fumigatus enolase, AfEno1, which was also characterized as fungal allergen, as a surface ligand for human plasma complement regulators. AfEno1 binds factor H, factor-H-like protein 1 (FHL-1), C4b binding protein (C4BP), and plasminogen. Factor H attaches to AfEno1 via two regions, via short conserved repeats (SCRs) 6–7 and 19–20, and FHL-1 contacts AfEno1 via SCRs 6–7. Both regulators when bound to AfEno1 retain cofactor activity and assist in C3b inactivation. Similarly, the classical pathway regulator C4BP binds to AfEno1 and bound to AfEno1; C4BP assists in C4b inactivation. Plasminogen which binds to AfEno1 via lysine residues is accessible for the tissue-type plasminogen activator (tPA), and active plasmin cleaves the chromogenic substrate S2251, degrades fibrinogen, and inactivates C3 and C3b. Plasmin attached to swollen A. fumigatus conidia damages human A549 lung epithelial cells, reduces the cellular metabolic activity, and induces cell retraction, which results in exposure of the extracellular matrix. Thus, A. fumigatus AfEno1 is a moonlighting protein and virulence factor which recruits several human regulators. The attached human regulators allow the fungal pathogen to control complement at the level of C3 and to damage endothelial cell layers and tissue components. |
| first_indexed | 2024-12-10T04:53:27Z |
| format | Article |
| id | doaj.art-4606800eeab44425a3ef7b2289e58cbd |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T04:53:27Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4606800eeab44425a3ef7b2289e58cbd2022-12-22T02:01:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-11-011010.3389/fimmu.2019.02573477768Enolase From Aspergillus fumigatus Is a Moonlighting Protein That Binds the Human Plasma Complement Proteins Factor H, FHL-1, C4BP, and PlasminogenPrasad Dasari0Naile Koleci1Iordana A. Shopova2Dirk Wartenberg3Niklas Beyersdorf4Stefanie Dietrich5Alfredo Sahagún-Ruiz6Marc Thilo Figge7Marc Thilo Figge8Christine Skerka9Axel A. Brakhage10Axel A. Brakhage11Peter F. Zipfel12Peter F. Zipfel13Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, GermanyDepartment of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, GermanyDepartment of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, GermanyDepartment of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, GermanyInstitute for Virology and Immunobiology, University of Würzburg, Würzburg, GermanyResearch Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, GermanyLaboratorio de Inmunología Molecular, Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City, MexicoResearch Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, GermanyInstitute of Microbiology, Friedrich Schiller University, Jena, GermanyDepartment of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, GermanyDepartment of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, GermanyInstitute of Microbiology, Friedrich Schiller University, Jena, GermanyDepartment of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, GermanyInstitute of Microbiology, Friedrich Schiller University, Jena, GermanyThe opportunistic fungal pathogen Aspergillus fumigatus can cause severe infections, particularly in immunocompromised individuals. Upon infection, A. fumigatus faces the powerful and directly acting immune defense of the human host. The mechanisms on how A. fumigatus evades innate immune attack and complement are still poorly understood. Here, we identify A. fumigatus enolase, AfEno1, which was also characterized as fungal allergen, as a surface ligand for human plasma complement regulators. AfEno1 binds factor H, factor-H-like protein 1 (FHL-1), C4b binding protein (C4BP), and plasminogen. Factor H attaches to AfEno1 via two regions, via short conserved repeats (SCRs) 6–7 and 19–20, and FHL-1 contacts AfEno1 via SCRs 6–7. Both regulators when bound to AfEno1 retain cofactor activity and assist in C3b inactivation. Similarly, the classical pathway regulator C4BP binds to AfEno1 and bound to AfEno1; C4BP assists in C4b inactivation. Plasminogen which binds to AfEno1 via lysine residues is accessible for the tissue-type plasminogen activator (tPA), and active plasmin cleaves the chromogenic substrate S2251, degrades fibrinogen, and inactivates C3 and C3b. Plasmin attached to swollen A. fumigatus conidia damages human A549 lung epithelial cells, reduces the cellular metabolic activity, and induces cell retraction, which results in exposure of the extracellular matrix. Thus, A. fumigatus AfEno1 is a moonlighting protein and virulence factor which recruits several human regulators. The attached human regulators allow the fungal pathogen to control complement at the level of C3 and to damage endothelial cell layers and tissue components.https://www.frontiersin.org/article/10.3389/fimmu.2019.02573/fullcomplement factor Hmoonlightingimmune evasionplasminogenblocking phagocytosis |
| spellingShingle | Prasad Dasari Naile Koleci Iordana A. Shopova Dirk Wartenberg Niklas Beyersdorf Stefanie Dietrich Alfredo Sahagún-Ruiz Marc Thilo Figge Marc Thilo Figge Christine Skerka Axel A. Brakhage Axel A. Brakhage Peter F. Zipfel Peter F. Zipfel Enolase From Aspergillus fumigatus Is a Moonlighting Protein That Binds the Human Plasma Complement Proteins Factor H, FHL-1, C4BP, and Plasminogen Frontiers in Immunology complement factor H moonlighting immune evasion plasminogen blocking phagocytosis |
| title | Enolase From Aspergillus fumigatus Is a Moonlighting Protein That Binds the Human Plasma Complement Proteins Factor H, FHL-1, C4BP, and Plasminogen |
| title_full | Enolase From Aspergillus fumigatus Is a Moonlighting Protein That Binds the Human Plasma Complement Proteins Factor H, FHL-1, C4BP, and Plasminogen |
| title_fullStr | Enolase From Aspergillus fumigatus Is a Moonlighting Protein That Binds the Human Plasma Complement Proteins Factor H, FHL-1, C4BP, and Plasminogen |
| title_full_unstemmed | Enolase From Aspergillus fumigatus Is a Moonlighting Protein That Binds the Human Plasma Complement Proteins Factor H, FHL-1, C4BP, and Plasminogen |
| title_short | Enolase From Aspergillus fumigatus Is a Moonlighting Protein That Binds the Human Plasma Complement Proteins Factor H, FHL-1, C4BP, and Plasminogen |
| title_sort | enolase from aspergillus fumigatus is a moonlighting protein that binds the human plasma complement proteins factor h fhl 1 c4bp and plasminogen |
| topic | complement factor H moonlighting immune evasion plasminogen blocking phagocytosis |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02573/full |
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