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Lipid metabolism in Chlamydia trachomatis-infected cells: Directed trafficking of Golgi-derived sphingolipids to the chlamydial inclusion

Host-Parasite Interactions Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT 59840, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 06/1995; 92(11):4877-81. DOI: 10.1073/pnas.92.11.4877
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ABSTRACT Chlamydia trachomatis undergoes its entire life cycle within an uncharacterized intracellular vesicle that does not fuse with lysosomes. We used a fluorescent Golgi-specific probe, (N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]) aminocaproylsphingosine (C6-NBD-Cer), in conjunction with conventional fluorescence or confocal microscopy to identify interactions between the Golgi apparatus and the chlamydial inclusion. We observed not only a close physical association between the Golgi apparatus and the chlamydial inclusion but the eventual presence of a metabolite of this fluorescent probe associated with the chlamydiae themselves. Sphingomyelin, endogenously synthesized from C6-NBD-Cer, was specifically transported to the inclusion and incorporated into the cell wall of the intracellular chlamydiae. Incorporation of the fluorescent sphingolipid by chlamydiae was inhibited by brefeldin A. Chlamydiae therefore occupy a vesicle distal to the Golgi apparatus that receives anterograde vesicular traffic from the Golgi normally bound for the plasma membrane. Collectively, the data suggest that the chlamydial inclusion may represent a unique compartment within the trans-Golgi network.

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    • "seven in C. trachomatis). Due to its high immunogenicity in guinea pigs, IncA of C. caviae was the first Inc protein to be discovered (Rockey, Heinzen and Hackstadt 1995). While the members of this protein family display little general sequence similarity, they share a characteristic bilobed hydrophobic domain of 60–80 amino acid residues. "
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    ABSTRACT: Chlamydia (C.) psittaci is an economically relevant pathogen in poultry and pet birds, where it causes psittacosis/ornithosis, and also a human pathogen causing atypical pneumonia after zoonotic transmission. Despite its well-documented prevalence, the agent has received less attention by researchers than other Chlamydia spp. in the last decades. In the present paper, we review recently published data on C. psittaci infection and attempt to single out characteristic features distinguishing it from related chlamydial agents. It is remarkable that C. psittaci is particularly efficient in disseminating in the host organism causing systemic disease, which occasionally can take a fulminant course. At the cellular level, the pathogen's broad host cell spectrum (from epithelial cells to macrophages), its rapid entry and fast replication, proficient use of intracellular transport routes to mitochondria and the Golgi apparatus, the pronounced physical association of chlamydial inclusions with energy-providing cell compartments, as well as the subversive regulation of host cell survival during productive and persistent states facilitate the characteristic efficient growth and successful host-to-host spread of C. psittaci. At the molecular level, the pathogen was shown to upregulate essential chlamydial genes when facing the host immune response. We hypothesize that this capacity, in concert with expression of specific effectors of the type III secretion system and efficient suppression of selected host defense signals, contributes to successful establishment of the infection in the host. Concerning the immunology of host-pathogen interactions, C. psittaci has been shown to distinguish itself by coping more efficiently than other chlamydiae with pro-inflammatory mediators during early host response, which can, to some extent, explain the effective evasion and adaptation strategies of this bacterium. We conclude that thorough analysis of the large number of whole-genome sequences already available will be essential to identify genetic markers of the species-specific features and trigger more in-depth studies in cellular and animal models to address such vital topics as treatment and vaccination. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    Pathogens and Disease 12/2014; 73(1). DOI:10.1093/femspd/ftu007 · 2.55 Impact Factor
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    • "During growth and replication within infected cells, Chlamydia acquires cholesterol and sphingolipids from the host via vesicular (Hackstadt et al., 1995; 1996; Carabeo et al., 2003; Beatty, 2006; Heuer et al., 2009; Elwell et al., 2011) and non-vesicular transport (Derre Fig. 8. HeLa cells were transfected with GFP-V-RS plasmids encoding two ABCA1-specific shRNAs or a control shRNA (A). Twenty-four hours post transfection the cells were infected with C. trachomatis serovar D and the cells were subsequently fixed with 4% paraformaldehyde in PBS at 48 h PI. "
    Dataset: Cox et al
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    • "During growth and replication within infected cells, Chlamydia acquires cholesterol and sphingolipids from the host via vesicular (Hackstadt et al., 1995; 1996; Carabeo et al., 2003; Beatty, 2006; Heuer et al., 2009; Elwell et al., 2011) and non-vesicular transport (Derre Fig. 8. HeLa cells were transfected with GFP-V-RS plasmids encoding two ABCA1-specific shRNAs or a control shRNA (A). Twenty-four hours post transfection the cells were infected with C. trachomatis serovar D and the cells were subsequently fixed with 4% paraformaldehyde in PBS at 48 h PI. "
    Dataset: Cox et al
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