The intracellular bacterium Orientia tsutsugamushi uses the autotransporter ScaC to activate BICD adaptors for dynein-based motility
Abstract The intracellular bacterium Orientia tsutsugamushi relies on the microtubule cytoskeleton and the motor protein dynein to traffic to the perinuclear region within infected cells. However, it remains unclear how the bacterium is coupled to the dynein machinery and how transport is regulated....
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61105-5 |
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| author | Giulia Manigrasso Kittirat Saharat Panjaporn Chaichana Chitrasak Kullapanich Sharanjeet Atwal Jerome Boulanger Tomos E. Morgan Holger Kramer Jeanne Salje Andrew P. Carter |
| author_facet | Giulia Manigrasso Kittirat Saharat Panjaporn Chaichana Chitrasak Kullapanich Sharanjeet Atwal Jerome Boulanger Tomos E. Morgan Holger Kramer Jeanne Salje Andrew P. Carter |
| author_sort | Giulia Manigrasso |
| collection | DOAJ |
| description | Abstract The intracellular bacterium Orientia tsutsugamushi relies on the microtubule cytoskeleton and the motor protein dynein to traffic to the perinuclear region within infected cells. However, it remains unclear how the bacterium is coupled to the dynein machinery and how transport is regulated. Here, we discover that O. tsutsugamushi uses its autotransporter protein ScaC to recruit the dynein adaptors BICD1 and BICD2 for movement to the perinucleus. We show that ScaC is sufficient to engage dynein-based motility in the absence of other bacterial proteins and that BICD1 and BICD2 are required for efficient movement of O. tsutsugamushi during infection. Using TIRF single-molecule assays, we demonstrate that ScaC induces BICD2 to adopt an open conformation which activates the assembly of dynein-dynactin complexes. Our results reveal a role for BICD adaptors during bacterial infection and provide mechanistic insights into the life cycle of an important human pathogen. |
| format | Article |
| id | doaj-art-e9fe58261c2e4f89bb6dc218f317c24e |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e9fe58261c2e4f89bb6dc218f317c24e2025-08-20T04:01:35ZengNature PortfolioNature Communications2041-17232025-07-0116111610.1038/s41467-025-61105-5The intracellular bacterium Orientia tsutsugamushi uses the autotransporter ScaC to activate BICD adaptors for dynein-based motilityGiulia Manigrasso0Kittirat Saharat1Panjaporn Chaichana2Chitrasak Kullapanich3Sharanjeet Atwal4Jerome Boulanger5Tomos E. Morgan6Holger Kramer7Jeanne Salje8Andrew P. Carter9MRC Laboratory of Molecular BiologyCambridge Institute for Medical Research, University of CambridgeCambridge Institute for Medical Research, University of CambridgeMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityLonzaMRC Laboratory of Molecular BiologyMRC Laboratory of Molecular BiologyMRC Laboratory of Molecular BiologyCambridge Institute for Medical Research, University of CambridgeMRC Laboratory of Molecular BiologyAbstract The intracellular bacterium Orientia tsutsugamushi relies on the microtubule cytoskeleton and the motor protein dynein to traffic to the perinuclear region within infected cells. However, it remains unclear how the bacterium is coupled to the dynein machinery and how transport is regulated. Here, we discover that O. tsutsugamushi uses its autotransporter protein ScaC to recruit the dynein adaptors BICD1 and BICD2 for movement to the perinucleus. We show that ScaC is sufficient to engage dynein-based motility in the absence of other bacterial proteins and that BICD1 and BICD2 are required for efficient movement of O. tsutsugamushi during infection. Using TIRF single-molecule assays, we demonstrate that ScaC induces BICD2 to adopt an open conformation which activates the assembly of dynein-dynactin complexes. Our results reveal a role for BICD adaptors during bacterial infection and provide mechanistic insights into the life cycle of an important human pathogen.https://doi.org/10.1038/s41467-025-61105-5 |
| spellingShingle | Giulia Manigrasso Kittirat Saharat Panjaporn Chaichana Chitrasak Kullapanich Sharanjeet Atwal Jerome Boulanger Tomos E. Morgan Holger Kramer Jeanne Salje Andrew P. Carter The intracellular bacterium Orientia tsutsugamushi uses the autotransporter ScaC to activate BICD adaptors for dynein-based motility Nature Communications |
| title | The intracellular bacterium Orientia tsutsugamushi uses the autotransporter ScaC to activate BICD adaptors for dynein-based motility |
| title_full | The intracellular bacterium Orientia tsutsugamushi uses the autotransporter ScaC to activate BICD adaptors for dynein-based motility |
| title_fullStr | The intracellular bacterium Orientia tsutsugamushi uses the autotransporter ScaC to activate BICD adaptors for dynein-based motility |
| title_full_unstemmed | The intracellular bacterium Orientia tsutsugamushi uses the autotransporter ScaC to activate BICD adaptors for dynein-based motility |
| title_short | The intracellular bacterium Orientia tsutsugamushi uses the autotransporter ScaC to activate BICD adaptors for dynein-based motility |
| title_sort | intracellular bacterium orientia tsutsugamushi uses the autotransporter scac to activate bicd adaptors for dynein based motility |
| url | https://doi.org/10.1038/s41467-025-61105-5 |
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