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The intracellular bacterium Orientia tsutsugamushi uses the autotransporter ScaC to activate BICD adaptors for dynein-based motility

Author

Listed:
  • Giulia Manigrasso

    (MRC Laboratory of Molecular Biology)

  • Kittirat Saharat

    (University of Cambridge)

  • Panjaporn Chaichana

    (University of Cambridge)

  • Chitrasak Kullapanich

    (Mahidol University)

  • Sharanjeet Atwal

    (Lonza)

  • Jerome Boulanger

    (MRC Laboratory of Molecular Biology)

  • Tomos E. Morgan

    (MRC Laboratory of Molecular Biology)

  • Holger Kramer

    (MRC Laboratory of Molecular Biology)

  • Jeanne Salje

    (University of Cambridge
    Mahidol University
    University of Cambridge
    University of Cambridge)

  • Andrew P. Carter

    (MRC Laboratory of Molecular Biology)

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.

Suggested Citation

  • Giulia Manigrasso & Kittirat Saharat & Panjaporn Chaichana & Chitrasak Kullapanich & Sharanjeet Atwal & Jerome Boulanger & Tomos E. Morgan & Holger Kramer & Jeanne Salje & Andrew P. Carter, 2025. "The intracellular bacterium Orientia tsutsugamushi uses the autotransporter ScaC to activate BICD adaptors for dynein-based motility," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61105-5
    DOI: 10.1038/s41467-025-61105-5
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    References listed on IDEAS

    as
    1. Edith Gouin & Coumaran Egile & Pierre Dehoux & Véronique Villiers & Josephine Adams & Frank Gertler & Rong Li & Pascale Cossart, 2004. "The RickA protein of Rickettsia conorii activates the Arp2/3 complex," Nature, Nature, vol. 427(6973), pages 457-461, January.
    2. Sharanjeet Atwal & Jantana Wongsantichon & Suparat Giengkam & Kittirat Saharat & Yanin Jaiyen Pittayasathornthun & Suthida Chuenklin & Loo Chien Wang & Taerin Chung & Hyun Huh & Sang-Hyuk Lee & Radosl, 2022. "The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Yuen-Yan Chang & Camila Valenzuela & Arthur Lensen & Noelia Lopez-Montero & Saima Sidik & John Salogiannis & Jost Enninga & John Rohde, 2024. "Microtubules provide force to promote membrane uncoating in vacuolar escape for a cyto-invasive bacterial pathogen," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
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