Abstract
Productive developmental cycle of the obligate intracellular bacterial pathogen Chlamydia trachomatis depends on the interaction of the replicative vacuole, named the inclusion, with cellular organelles. We have recently reported the formation of ER-Inclusion membrane contact sites (MCSs), where the endoplasmic reticulum (ER) is in apposition to the inclusion membrane. These platforms contain the C. trachomatis inclusion membrane protein IncD, the mammalian ceramide transfer protein CERT and the ER resident proteins VAPA/B and were proposed to play a role in the non-vesicular trafficking of lipids to the inclusion. Here, we identify STIM1 as a novel component of ER-Inclusion MCSs. STIM1, an ER calcium (Ca2+) sensor that relocate to ER-Plasma Membrane (PM) MCSs upon Ca2+ store depletion, associated with C. trachomatis inclusion. STIM1, but not the general ER markers Rtn3C and Sec61ß, was enriched at the inclusion membrane. Ultra-structural studies demonstrated that STIM1 localized to ER-Inclusion MCSs. Time-course experiments showed that STIM1, CERT and VAPB co-localized throughout the developmental cycle. By contrast, Orai1, the PM Ca2+ channel that interacts with STIM1 at ER-PM MCSs, did not associate with C. trachomatis inclusion. Upon ER Ca2+ store depletion, a pool of STIM1 relocated to ER-PM MCSs, while the existing ER-Inclusion MCSs remained enriched in STIM1. Finally, we have identified the CAD domain, which mediates STIM1-Orai1 interaction, as the minimal domain required for STIM1 enrichment at ER-Inclusion MCSs. Altogether this study identifies STIM1 as a novel component of ER-C. trachomatis inclusion MCSs. We discuss the potential role(s) of STIM1 during the infection process.
Highlights
Chlamydia trachomatis is a Gram-negative obligate intracellular bacterial pathogen that infects ocular and genital epithelial surfaces
We show that STIM1 associates with C. trachomatis inclusion, where it co-localizes with CERT and VAPB at endoplasmic reticulum (ER)-Inclusion membrane contact sites (MCSs)
We investigated if any other known components of MCSs associated with the inclusion and found that STIM1, a component of ER-Plasma Membrane (PM) MCSs, was enriched at the C. trachomatis inclusion membrane (Fig 1)
Summary
Chlamydia trachomatis is a Gram-negative obligate intracellular bacterial pathogen that infects ocular and genital epithelial surfaces. Upon entry into the host cells, the bacteria reside in a membrane bound compartment, named the inclusion. C. trachomatis developmental cycle lasts 2 days and begins with the entry of the infectious form of the bacteria (i.e. EB, Elementary Body) into the host cell. STIM and ER-Chlamydia Inclusion Membrane Contact Sites. Body), C. trachomatis undergoes several rounds of bacterial replication, leading to the expansion of the inclusion. RBs start to transition back into EBs. The exit of EBs from the host cell completes the cycle and allows for infection of the neighboring cells [1, 2]
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