Microtubules provide force to promote membrane uncoating in vacuolar escape for a cyto-invasive bacterial pathogen
Abstract Intracellular bacterial pathogens gain entry to mammalian cells inside a vacuole derived from the host membrane. Some of them escape the bacteria-containing vacuole (BCV) and colonize the cytosol. Bacteria replicating within BCVs coopt the microtubule network to position it within infected...
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| Format: | Article |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45182-6 |
| _version_ | 1797274049951301632 |
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| author | Yuen-Yan Chang Camila Valenzuela Arthur Lensen Noelia Lopez-Montero Saima Sidik John Salogiannis Jost Enninga John Rohde |
| author_facet | Yuen-Yan Chang Camila Valenzuela Arthur Lensen Noelia Lopez-Montero Saima Sidik John Salogiannis Jost Enninga John Rohde |
| author_sort | Yuen-Yan Chang |
| collection | DOAJ |
| description | Abstract Intracellular bacterial pathogens gain entry to mammalian cells inside a vacuole derived from the host membrane. Some of them escape the bacteria-containing vacuole (BCV) and colonize the cytosol. Bacteria replicating within BCVs coopt the microtubule network to position it within infected cells, whereas the role of microtubules for cyto-invasive pathogens remains obscure. Here, we show that the microtubule motor cytoplasmic dynein-1 and specific activating adaptors are hijacked by the enterobacterium Shigella flexneri. These host proteins were found on infection-associated macropinosomes (IAMs) formed during Shigella internalization. We identified Rab8 and Rab13 as mediators of dynein recruitment and discovered that the Shigella effector protein IpaH7.8 promotes Rab13 retention on moving BCV membrane remnants, thereby facilitating membrane uncoating of the Shigella-containing vacuole. Moreover, the efficient unpeeling of BCV remnants contributes to a successful intercellular spread. Taken together, our work demonstrates how a bacterial pathogen subverts the intracellular transport machinery to secure a cytosolic niche. |
| first_indexed | 2024-03-07T14:52:50Z |
| format | Article |
| id | doaj.art-b50b0625dde648359113f818c3e4dba2 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:52:50Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-b50b0625dde648359113f818c3e4dba22024-03-05T19:36:55ZengNature PortfolioNature Communications2041-17232024-02-0115111210.1038/s41467-024-45182-6Microtubules provide force to promote membrane uncoating in vacuolar escape for a cyto-invasive bacterial pathogenYuen-Yan Chang0Camila Valenzuela1Arthur Lensen2Noelia Lopez-Montero3Saima Sidik4John Salogiannis5Jost Enninga6John Rohde7Dynamics of Host-Pathogen Interactions Unit, Institut Pasteur, and CNRS UMR 3691 Université de Paris CitéDynamics of Host-Pathogen Interactions Unit, Institut Pasteur, and CNRS UMR 3691 Université de Paris CitéDynamics of Host-Pathogen Interactions Unit, Institut Pasteur, and CNRS UMR 3691 Université de Paris CitéDynamics of Host-Pathogen Interactions Unit, Institut Pasteur, and CNRS UMR 3691 Université de Paris CitéDepartment of Microbiology and Immunology, Dalhousie UniversityDepartment of Cellular and Molecular Medicine, University of California San DiegoDynamics of Host-Pathogen Interactions Unit, Institut Pasteur, and CNRS UMR 3691 Université de Paris CitéDepartment of Microbiology and Immunology, Dalhousie UniversityAbstract Intracellular bacterial pathogens gain entry to mammalian cells inside a vacuole derived from the host membrane. Some of them escape the bacteria-containing vacuole (BCV) and colonize the cytosol. Bacteria replicating within BCVs coopt the microtubule network to position it within infected cells, whereas the role of microtubules for cyto-invasive pathogens remains obscure. Here, we show that the microtubule motor cytoplasmic dynein-1 and specific activating adaptors are hijacked by the enterobacterium Shigella flexneri. These host proteins were found on infection-associated macropinosomes (IAMs) formed during Shigella internalization. We identified Rab8 and Rab13 as mediators of dynein recruitment and discovered that the Shigella effector protein IpaH7.8 promotes Rab13 retention on moving BCV membrane remnants, thereby facilitating membrane uncoating of the Shigella-containing vacuole. Moreover, the efficient unpeeling of BCV remnants contributes to a successful intercellular spread. Taken together, our work demonstrates how a bacterial pathogen subverts the intracellular transport machinery to secure a cytosolic niche.https://doi.org/10.1038/s41467-024-45182-6 |
| spellingShingle | Yuen-Yan Chang Camila Valenzuela Arthur Lensen Noelia Lopez-Montero Saima Sidik John Salogiannis Jost Enninga John Rohde Microtubules provide force to promote membrane uncoating in vacuolar escape for a cyto-invasive bacterial pathogen Nature Communications |
| title | Microtubules provide force to promote membrane uncoating in vacuolar escape for a cyto-invasive bacterial pathogen |
| title_full | Microtubules provide force to promote membrane uncoating in vacuolar escape for a cyto-invasive bacterial pathogen |
| title_fullStr | Microtubules provide force to promote membrane uncoating in vacuolar escape for a cyto-invasive bacterial pathogen |
| title_full_unstemmed | Microtubules provide force to promote membrane uncoating in vacuolar escape for a cyto-invasive bacterial pathogen |
| title_short | Microtubules provide force to promote membrane uncoating in vacuolar escape for a cyto-invasive bacterial pathogen |
| title_sort | microtubules provide force to promote membrane uncoating in vacuolar escape for a cyto invasive bacterial pathogen |
| url | https://doi.org/10.1038/s41467-024-45182-6 |
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