Abstract
Many intracellular pathogens that replicate in special membrane bound compartments exploit cellular trafficking pathways by targeting small GTPases, including Rab proteins. Members of the Chlamydiaceae recruit a subset of Rab proteins to their inclusions, but the significance of these interactions is uncertain. Using RNA interference, we identified Rab6 and Rab11 as important regulators of Chlamydia infections. Depletion of either Rab6 or Rab11, but not the other Rab proteins tested, decreased the formation of infectious particles. We further examined the interplay between these Rab proteins and the Golgi matrix components golgin-84 and p115 with regard to Chlamydia-induced Golgi fragmentation. Silencing of the Rab proteins blocked Chlamydia-induced and golgin-84 knockdown-stimulated Golgi disruption, whereas Golgi fragmentation was unaffected in p115 depleted cells. Interestingly, p115-induced Golgi fragmentation could rescue Chlamydia propagation in Rab6 and Rab11 knockdown cells. Furthermore, transport of nutrients to Chlamydia, as monitored by BODIPY-Ceramide, was inhibited by Rab6 and Rab11 knockdown. Taken together, our results demonstrate that Rab6 and Rab11 are key regulators of Golgi stability and further support the notion that Chlamydia subverts Golgi structure to enhance its intracellular development.
Highlights
With an estimated 90 million new infections per year, Chlamydia trachomatis is the most frequently sexually transmitted bacterial species
EGFP tagged Rab1, Rab6 and Rab11 have previously been shown to associate with the C. trachomatis inclusion, whereas Rab5 and Rab10 are not recruited to the inclusion [28]
We assessed the impact of these Rab proteins on C. trachomatis replication by RNA interference (RNAi) loss-of-function analysis. short interfering RNAs (siRNAs) used were specific for distinct Rab isoforms
Summary
With an estimated 90 million new infections per year, Chlamydia trachomatis is the most frequently sexually transmitted bacterial species. Infections with the serovars D–K can cause pelvic inflammatory disease and inflammation of the endometrium and urethra [1,2]. Chronic or recurring infections with C. trachomatis are considered to cause infertility in women. Chlamydia remodel host cell components to fashion a membrane bound niche, termed the inclusion, via the secretion of bacterial proteins [5,6]. This special niche is distinct from the lysosomal degradation pathway but allows interactions with the Golgi apparatus (GA), multivesicular bodies and lipid droplets [7,8,9,10]. Uptake of different lipids including sphingolipids and phospholipids is known to be essential for Chlamydia development [11,12,13]; the role of host proteins in this process is still largely unknown
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