Chlamydia causes fragmentation of the Golgi compartment to ensure reproduction.
The obligate intracellular bacterium Chlamydia trachomatis survives and replicates within a membrane-bound vacuole, termed the inclusion, which intercepts host exocytic pathways to obtain nutrients. 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 apparatus. However, the mechanisms by which intracellular pathogens acquire host cell lipids are not well understood. 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.
Heuer
Dagmar
D
Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
Rejman Lipinski
Anette
A
Machuy
Nikolaus
N
Karlas
Alexander
A
Wehrens
Andrea
A
Siedler
Frank
F
Brinkmann
Volker
V
Meyer
Thomas F
TF
D023502:Chlamydia muridarum / Q000254:growth & development; D002692:Chlamydia trachomatis / Q000254:growth & development* / Q000472:pathogenicity*; D004847:Epithelial Cells / Q000382:microbiology / Q000473:pathology; D055785:Gene Knockdown Techniques; D006056:Golgi Apparatus / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D000077614:Golgi Matrix Proteins; D006367:HeLa Cells; D006801:Humans; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D033921:Vesicular Transport Proteins
C060042:GOLGA5 protein, human; D000077614:Golgi Matrix Proteins; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins