Letter | Published:

Chlamydia causes fragmentation of the Golgi compartment to ensure reproduction

Nature volume 457, pages 731735 (05 February 2009) | Download Citation

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Abstract

The obligate intracellular bacterium Chlamydia trachomatis survives and replicates within a membrane-bound vacuole, termed the inclusion, which intercepts host exocytic pathways to obtain nutrients1,2,3. Like many other intracellular pathogens, C. trachomatis has a marked requirement for host cell lipids, such as sphingolipids and cholesterol, produced in the endoplasmic reticulum and the Golgi apparatus4,5,6. However, the mechanisms by which intracellular pathogens acquire host cell lipids are not well understood1,2,3. In particular, no host cell protein responsible for transporting Golgi-derived lipids to the chlamydial inclusions has yet been identified. Here we show that Chlamydia infection in human epithelial cells induces Golgi fragmentation to generate Golgi ministacks surrounding the bacterial inclusion. Ministack formation is triggered by the proteolytic cleavage of the Golgi matrix protein golgin-84. Inhibition of golgin-84 truncation prevents Golgi fragmentation, causing a block in lipid acquisition and maturation of C. trachomatis. Golgi fragmentation by means of RNA-interference-mediated knockdown of distinct Golgi matrix proteins before infection enhances bacterial maturation. Our data functionally connect bacteria-induced golgin-84 cleavage, Golgi ministack formation, lipid acquisition and intracellular pathogen growth. We show that C. trachomatis subverts the structure and function of an entire host cell organelle for its own advantage.

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Acknowledgements

The authors would like to thank A. Greiser, C. Goosmann, B. Laube, M. Wicht and E. Ziska for technical support; M. A. De Matteis for the gift of the GFP–GM130 fusion plasmid; H. P. Hauri for the provision of the anti-GPP130 antibody and helpful discussions; and K. Astrahantseff, S. and J. Heuer, T. Wolff and L. Ogilvie for critically reading the manuscript and helpful suggestions. This work was financially supported by the Senate of Berlin and the BMBF through the RiNA Network.

Author information

Affiliations

  1. Department of Molecular Biology,

    • Dagmar Heuer
    • , Anette Rejman Lipinski
    • , Nikolaus Machuy
    • , Alexander Karlas
    • , Andrea Wehrens
    •  & Thomas F. Meyer
  2. Microscopy Core Facility, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany

    • Volker Brinkmann
  3. Department of Membrane Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany

    • Frank Siedler

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Corresponding author

Correspondence to Thomas F. Meyer.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Figures 1-17 with Legends and Supplementary Table 1 which summarizes truncated golgin-84 expressing cell line, plasmids and primers.

Videos

  1. 1.

    Supplementary Movie 1

    Supplementary Movie 1 shows GM130-GFP expressing cells infected with C.trachomatis to reveal GA disruption during the infection period. The time lapse covers about 12 h. By following cells during the course of the movie, it is evident that the GA is dispersed during infection.

  2. 2.

    Supplementary Movie 2

    Supplementary Movie 2 shows ceramide trafficking in infected cells. BODIPY FL C5-ceramide transport into the inclusion. Time-lapse images of HeLa cells infected with C. trachomatis (MOI = 2) for 26 h. Labelled ceramide was added 1 to 2 minutes after starting image acquisition. The assigned numbers represent the time elapsed.

  3. 3.

    Supplementary Movie 3

    Supplementary Movie 3 shows ceramide trafficking in infected cells treated with Z-WEHD-FMK. BODIPY FL C5-ceramide transport into the inclusion is inhibited by treatment with Z-WEHD-FMK. Time-lapse images of HeLa cells infected with C. trachomatis (MOI = 2) treated with inhibitor 9 h p.i. Image acquisition was started at 27 h p.i. and labelled ceramide was added 1 to 2 minutes after starting the acquisition. The assigned numbers represent the time elapsed.

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DOI

https://doi.org/10.1038/nature07578

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