Chlamydia causes fragmentation of the Golgi compartment to ensure reproduction

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 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.

Influenza infection modulates vesicular trafficking and induces Golgi complex disruption

“…Using the Golgi markers, GM130 and b-COP we found that virus infection results in Golgi fragmentation and dispersion. The breakdown and dispersal of the Golgi stacks has been reported to lower the efficiency of protein export [29] and can facilitate the replication of some intracellular pathogens [13]. Herpes Simplex Virus-1-induced Golgi fragmentation has been found to increase the efficiency of virion release into the extracellular space [5].…”

“…NOC inhibits microtubule polymerization which leads to trans-Golgi network fragmentation, whereas BFA disrupt the anterograde transport, and forms the trans-Golgi tubular network [9]. ZWEHD is an inhibitor of inflammatory caspases and inhibits Golgi fragmentation [13]. These inhibitors of vesicle function and integrity reduce virus replication as evidenced by a reduction in virus titer.…”

“…While the mechanism of this inhibition by IFV is unclear, studies with other viruses indicate that the Golgi can fragment or disperse during infection [7,13], and this may result in inhibition of host protein processing and concomitant promotion of viral replication [5,20,40]. The Golgi normally undergoes fragmentation during mitosis as well as in apoptotic cells.…”

Role of Phosphatidylinositol 4-Phosphate (PI4P) and Its Binding Protein GOLPH3 in Hepatitis C Virus Secretion

“…The fragmentation of the Golgi in HCV correlates with the decrease in general secretory capacity of the infected cell but further implicates the organelle in important viral processes and hints toward sequestration of secretory components at sites of viral assembly. Golgi disruption and decrease in secretory capacity of host cells is a peculiar feature of many infectious agents such as Chlamydia, poliovirus, and rhinovirus 1A, where the Golgi membranes serve an important role in viral replication and morphogenesis (57)(58)(59)(60).…”

Identification of host factors required for Yersinia pestis macrophage intracellular survival and their impact on vacuole maturation, acidification and trafficking.

“…Inhibition of Rab11a, using a dominant negative form which cannot tether to the ApV, they attenuate A. phagocytophilum intracellular survival by >10% at 5 h post-infection in HL-60 cells [191]. RNAi knockdown of Rab11a in HeLa and HEp-2 cells, prevents Chlamydia trachomatis reversion from the metabolically active reticulate body into the inert infectious elementary body by blocking the bacteria's ability to disrupt the Golgi [245][246][247]. Excitingly, when we re-visited the Coxiella burnetii genome-wide RNAi screen data (another pathogen residing in a pathogen containing vacuole termed the CCV) we noticed that inhibition of Rab11b also prevented bacterial replication [131].…”