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Coxiella burnetii manipulates the lysosomal protease cathepsin B to facilitate intracellular success

Author

Listed:
  • Lauren E. Bird

    (The University of Melbourne
    Monash University)

  • Bangyan Xu

    (The University of Melbourne)

  • Andrew D. Hobbs

    (Monash University)

  • Alexander R. Ziegler

    (The University of Melbourne)

  • Nichollas E. Scott

    (The University of Melbourne)

  • Patrice Newton

    (The University of Melbourne
    Monash University)

  • David R. Thomas

    (Monash University)

  • Laura E. Edgington-Mitchell

    (The University of Melbourne)

  • Hayley J. Newton

    (The University of Melbourne
    Monash University)

Abstract

The obligate intracellular bacterium Coxiella burnetii establishes an intracellular replicative niche termed the Coxiella-containing vacuole (CCV), which has been characterised as a bacterially modified phagolysosome. How C. burnetii withstands the acidic and degradative properties of this compartment is not well understood. We demonstrate that the key lysosomal protease cathepsin B is actively and selectively removed from C. burnetii-infected cells through a mechanism involving the Dot/Icm type IV-B secretion system effector CvpB. Overexpression of cathepsin B leads to defects in CCV biogenesis and bacterial replication, indicating that removal of this protein represents a strategy to reduce the hostility of the intracellular niche. In addition, we show that C. burnetii infection of mammalian cells induces the secretion of a wider cohort of lysosomal proteins, including cathepsin B, to the extracellular milieu via a mechanism dependent on retrograde traffic. This study reveals that C. burnetii is actively modulating the hydrolase cohort of its replicative niche to promote intracellular success and demonstrates that infection incites the secretory pathway to maintain lysosomal homoeostasis.

Suggested Citation

  • Lauren E. Bird & Bangyan Xu & Andrew D. Hobbs & Alexander R. Ziegler & Nichollas E. Scott & Patrice Newton & David R. Thomas & Laura E. Edgington-Mitchell & Hayley J. Newton, 2025. "Coxiella burnetii manipulates the lysosomal protease cathepsin B to facilitate intracellular success," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59283-3
    DOI: 10.1038/s41467-025-59283-3
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    References listed on IDEAS

    as
    1. Weichao Zhang & Xi Yang & Yingxiang Li & Linchen Yu & Bokai Zhang & Jianchao Zhang & Woo Jung Cho & Varsha Venkatarangan & Liang Chen & Bala Bharathi Burugula & Sarah Bui & Yanzhuang Wang & Cunming Du, 2022. "GCAF(TMEM251) regulates lysosome biogenesis by activating the mannose-6-phosphate pathway," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
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