Executioner caspases degrade essential mediators of pathogen-host interactions to inhibit growth of intracellular Listeria monocytogenes
Abstract Cell death mediated by executioner caspases is essential during organ development and for organismal homeostasis. The mechanistic role of activated executioner caspases in antibacterial defense during infections with intracellular bacteria, such as Listeria monocytogenes, remains elusive. C...
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| Format: | Article |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07365-x |
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| author | Marilyne Lavergne Raffael Schaerer Sara De Grandis Safaa Bouheraoua Oluwadamilola Adenuga Tanja Muralt Tiffany Schaerer Léa Chèvre Alessandro Failla Patricia Matthey Michael Stumpe Dieter Kressler Pierre-Yves Mantel Michael Walch |
| author_facet | Marilyne Lavergne Raffael Schaerer Sara De Grandis Safaa Bouheraoua Oluwadamilola Adenuga Tanja Muralt Tiffany Schaerer Léa Chèvre Alessandro Failla Patricia Matthey Michael Stumpe Dieter Kressler Pierre-Yves Mantel Michael Walch |
| author_sort | Marilyne Lavergne |
| collection | DOAJ |
| description | Abstract Cell death mediated by executioner caspases is essential during organ development and for organismal homeostasis. The mechanistic role of activated executioner caspases in antibacterial defense during infections with intracellular bacteria, such as Listeria monocytogenes, remains elusive. Cell death upon intracellular bacterial infections is considered altruistic to deprive the pathogens of their protective niche. To establish infections in a human host, Listeria monocytogenes deploy virulence mediators, including membranolytic listeriolysin O (LLO) and the invasion associated protein p60 (Iap), allowing phagosomal escape, intracellular replication and cell-to-cell spread. Here, by means of chemical and genetical modifications, we show that the executioner caspases-3 and -7 efficiently inhibit growth of intracellular Listeria monocytogenes in host cells. Comprehensive proteomics revealed multiple caspase-3 substrates in the Listeria secretome, including LLO, Iap and various other proteins crucially involved in pathogen-host interactions. Listeria secreting caspase-uncleavable LLO or Iap gained significant growth advantage in epithelial cells. With that, we uncovered an underappreciated defense barrier and a non-canonical role of executioner caspases to degrade virulence mediators, thus impairing intracellular Listeria growth. |
| format | Article |
| id | doaj-art-54d569e943854972b9908b8885871553 |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-54d569e943854972b9908b88858715532025-02-02T12:44:54ZengNature Publishing GroupCell Death and Disease2041-48892025-01-0116111710.1038/s41419-025-07365-xExecutioner caspases degrade essential mediators of pathogen-host interactions to inhibit growth of intracellular Listeria monocytogenesMarilyne Lavergne0Raffael Schaerer1Sara De Grandis2Safaa Bouheraoua3Oluwadamilola Adenuga4Tanja Muralt5Tiffany Schaerer6Léa Chèvre7Alessandro Failla8Patricia Matthey9Michael Stumpe10Dieter Kressler11Pierre-Yves Mantel12Michael Walch13Faculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy unit, University of FribourgFaculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy unit, University of FribourgFaculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy unit, University of FribourgFaculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy unit, University of FribourgFaculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy unit, University of FribourgFaculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy unit, University of FribourgFaculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy unit, University of FribourgFaculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy unit, University of FribourgFaculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy unit, University of FribourgFaculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy unit, University of FribourgFaculty of Science and Medicine, Department of Biology, Metabolomics and Proteomics Platform, University of FribourgFaculty of Science and Medicine, Department of Biology, Metabolomics and Proteomics Platform, University of FribourgFaculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy unit, University of FribourgFaculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy unit, University of FribourgAbstract Cell death mediated by executioner caspases is essential during organ development and for organismal homeostasis. The mechanistic role of activated executioner caspases in antibacterial defense during infections with intracellular bacteria, such as Listeria monocytogenes, remains elusive. Cell death upon intracellular bacterial infections is considered altruistic to deprive the pathogens of their protective niche. To establish infections in a human host, Listeria monocytogenes deploy virulence mediators, including membranolytic listeriolysin O (LLO) and the invasion associated protein p60 (Iap), allowing phagosomal escape, intracellular replication and cell-to-cell spread. Here, by means of chemical and genetical modifications, we show that the executioner caspases-3 and -7 efficiently inhibit growth of intracellular Listeria monocytogenes in host cells. Comprehensive proteomics revealed multiple caspase-3 substrates in the Listeria secretome, including LLO, Iap and various other proteins crucially involved in pathogen-host interactions. Listeria secreting caspase-uncleavable LLO or Iap gained significant growth advantage in epithelial cells. With that, we uncovered an underappreciated defense barrier and a non-canonical role of executioner caspases to degrade virulence mediators, thus impairing intracellular Listeria growth.https://doi.org/10.1038/s41419-025-07365-x |
| spellingShingle | Marilyne Lavergne Raffael Schaerer Sara De Grandis Safaa Bouheraoua Oluwadamilola Adenuga Tanja Muralt Tiffany Schaerer Léa Chèvre Alessandro Failla Patricia Matthey Michael Stumpe Dieter Kressler Pierre-Yves Mantel Michael Walch Executioner caspases degrade essential mediators of pathogen-host interactions to inhibit growth of intracellular Listeria monocytogenes Cell Death and Disease |
| title | Executioner caspases degrade essential mediators of pathogen-host interactions to inhibit growth of intracellular Listeria monocytogenes |
| title_full | Executioner caspases degrade essential mediators of pathogen-host interactions to inhibit growth of intracellular Listeria monocytogenes |
| title_fullStr | Executioner caspases degrade essential mediators of pathogen-host interactions to inhibit growth of intracellular Listeria monocytogenes |
| title_full_unstemmed | Executioner caspases degrade essential mediators of pathogen-host interactions to inhibit growth of intracellular Listeria monocytogenes |
| title_short | Executioner caspases degrade essential mediators of pathogen-host interactions to inhibit growth of intracellular Listeria monocytogenes |
| title_sort | executioner caspases degrade essential mediators of pathogen host interactions to inhibit growth of intracellular listeria monocytogenes |
| url | https://doi.org/10.1038/s41419-025-07365-x |
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