Function and firing of the Streptomyces coelicolor contractile injection system requires the membrane protein CisA

Bacterial contractile injection systems (CIS) are phage tail-like macromolecular complexes that mediate cell-cell interactions by injecting effector proteins into target cells. CIS from Streptomyces coelicolor (CISSc) are localized in the cytoplasm. Under stress, they induce cell death and impact th...

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Main Authors: Bastien Casu, Joseph W Sallmen, Peter E Haas, Govind Chandra, Pavel Afanasyev, Jingwei Xu, Martin Pilhofer, Susan Schlimpert
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2025-07-01
Series:eLife
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Online Access:https://elifesciences.org/articles/104064
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author Bastien Casu
Joseph W Sallmen
Peter E Haas
Govind Chandra
Pavel Afanasyev
Jingwei Xu
Martin Pilhofer
Susan Schlimpert
author_facet Bastien Casu
Joseph W Sallmen
Peter E Haas
Govind Chandra
Pavel Afanasyev
Jingwei Xu
Martin Pilhofer
Susan Schlimpert
author_sort Bastien Casu
collection DOAJ
description Bacterial contractile injection systems (CIS) are phage tail-like macromolecular complexes that mediate cell-cell interactions by injecting effector proteins into target cells. CIS from Streptomyces coelicolor (CISSc) are localized in the cytoplasm. Under stress, they induce cell death and impact the Streptomyces life cycle. It remains unknown, however, whether CISSc require accessory proteins to directly interact with the cytoplasmic membrane to function. Here, we characterize the putative membrane adaptor CisA, a conserved factor in CIS gene clusters across Streptomyces species. We show by cryo-electron tomography imaging and in vivo assays that CISSc contraction and function depend on CisA. Using single-particle cryo-electron microscopy, we provide an atomic model of the extended CISSc apparatus; however, CisA is not part of the complex. Instead, our findings show that CisA is a membrane protein with a cytoplasmic N-terminus predicted to interact with CISSc components, thereby providing a possible mechanism for mediating CISSc recruitment to the membrane and subsequent firing. Our work shows that CIS function in multicellular bacteria is distinct from type VI secretion systems and extracellular CIS, and possibly evolved due to the role CISSc play in regulated cell death.
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spelling doaj-art-6aaaa8472c994c2680b1ff63b1daca052025-08-20T03:33:15ZengeLife Sciences Publications LtdeLife2050-084X2025-07-011410.7554/eLife.104064Function and firing of the Streptomyces coelicolor contractile injection system requires the membrane protein CisABastien Casu0https://orcid.org/0000-0003-3508-6804Joseph W Sallmen1Peter E Haas2Govind Chandra3https://orcid.org/0000-0002-7882-6676Pavel Afanasyev4https://orcid.org/0000-0002-6353-6895Jingwei Xu5Martin Pilhofer6https://orcid.org/0000-0002-3649-3340Susan Schlimpert7https://orcid.org/0000-0001-6364-8056Department of Biology, Institute of Molecular Biology & Biophysics, Eidgenössische Technische Hochschule Zürich, Zurich, SwitzerlandJohn Innes Centre, Department of Molecular Microbiology, Norwich Research Park, Norwich, United KingdomDepartment of Biology, Institute of Molecular Biology & Biophysics, Eidgenössische Technische Hochschule Zürich, Zurich, SwitzerlandJohn Innes Centre, Department of Molecular Microbiology, Norwich Research Park, Norwich, United KingdomCryo-EM Knowledge Hub, Eidgenössische Technische Hochschule Zürich, Zurich, SwitzerlandDepartment of Biology, Institute of Molecular Biology & Biophysics, Eidgenössische Technische Hochschule Zürich, Zurich, SwitzerlandDepartment of Biology, Institute of Molecular Biology & Biophysics, Eidgenössische Technische Hochschule Zürich, Zurich, SwitzerlandJohn Innes Centre, Department of Molecular Microbiology, Norwich Research Park, Norwich, United Kingdom; Centre for Microbial Interactions, Norwich Research Park, Norwich, United KingdomBacterial contractile injection systems (CIS) are phage tail-like macromolecular complexes that mediate cell-cell interactions by injecting effector proteins into target cells. CIS from Streptomyces coelicolor (CISSc) are localized in the cytoplasm. Under stress, they induce cell death and impact the Streptomyces life cycle. It remains unknown, however, whether CISSc require accessory proteins to directly interact with the cytoplasmic membrane to function. Here, we characterize the putative membrane adaptor CisA, a conserved factor in CIS gene clusters across Streptomyces species. We show by cryo-electron tomography imaging and in vivo assays that CISSc contraction and function depend on CisA. Using single-particle cryo-electron microscopy, we provide an atomic model of the extended CISSc apparatus; however, CisA is not part of the complex. Instead, our findings show that CisA is a membrane protein with a cytoplasmic N-terminus predicted to interact with CISSc components, thereby providing a possible mechanism for mediating CISSc recruitment to the membrane and subsequent firing. Our work shows that CIS function in multicellular bacteria is distinct from type VI secretion systems and extracellular CIS, and possibly evolved due to the role CISSc play in regulated cell death.https://elifesciences.org/articles/104064bacterial developmentphage tail-like structuresregulated cell deathmulticellularityStreptomycescontractile injection systems
spellingShingle Bastien Casu
Joseph W Sallmen
Peter E Haas
Govind Chandra
Pavel Afanasyev
Jingwei Xu
Martin Pilhofer
Susan Schlimpert
Function and firing of the Streptomyces coelicolor contractile injection system requires the membrane protein CisA
eLife
bacterial development
phage tail-like structures
regulated cell death
multicellularity
Streptomyces
contractile injection systems
title Function and firing of the Streptomyces coelicolor contractile injection system requires the membrane protein CisA
title_full Function and firing of the Streptomyces coelicolor contractile injection system requires the membrane protein CisA
title_fullStr Function and firing of the Streptomyces coelicolor contractile injection system requires the membrane protein CisA
title_full_unstemmed Function and firing of the Streptomyces coelicolor contractile injection system requires the membrane protein CisA
title_short Function and firing of the Streptomyces coelicolor contractile injection system requires the membrane protein CisA
title_sort function and firing of the streptomyces coelicolor contractile injection system requires the membrane protein cisa
topic bacterial development
phage tail-like structures
regulated cell death
multicellularity
Streptomyces
contractile injection systems
url https://elifesciences.org/articles/104064
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