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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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.
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.
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.
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.
About this article
Nature Reviews Microbiology (2016)