Abstract
Chlamydia trachomatis is an important human pathogen that replicates inside the infected host cell in a unique vacuole, the inclusion. The formation of this intracellular bacterial niche is essential for productive Chlamydia infections. Despite its importance for Chlamydia biology, a holistic view on the protein composition of the inclusion, including its membrane, is currently missing. Here we describe the host cell-derived proteome of isolated C. trachomatis inclusions by quantitative proteomics. Computational analysis indicated that the inclusion is a complex intracellular trafficking platform that interacts with host cells’ antero- and retrograde trafficking pathways. Furthermore, the inclusion is highly enriched for sorting nexins of the SNX-BAR retromer, a complex essential for retrograde trafficking. Functional studies showed that in particular, SNX5 controls the C. trachomatis infection and that retrograde trafficking is essential for infectious progeny formation. In summary, these findings suggest that C. trachomatis hijacks retrograde pathways for effective infection.
Highlights
With 100 million new infections per year, Chlamydia trachomatis is the most frequently sexually transmitted bacterial pathogen world-wide [1]
We showed that the inclusion is a complex intracellular trafficking platform that is well embedded into the organellar network and interacts with host cells’ antero
Using LC-MS/MS based proteomics combined with ss isotope labeling by amino acids in cell culture (SILAC), we identified 351 host cell proteins that are significantly enriched in the proteome of isolated inclusions, representing the host cell-derived Chlamydia inclusion proteome
Summary
With 100 million new infections per year, Chlamydia trachomatis is the most frequently sexually transmitted bacterial pathogen world-wide [1]. EBs differentiate into RBs, which replicate inside the growing inclusion. At mid-infection time points the inclusion is packed with replicating RBs that start to re-differentiate into EBs [2]. The surrounding inclusion membrane is the interface between the bacteria and the host cell. This membrane is actively modified by insertion of bacterial proteins and is not permissive for diffusion of molecules of 520 Da and larger [3]. It contains classical bacterial inclusion proteins of the Inc-protein family as well as non-classical Inc proteins [4]. A growing number of cellular proteins have been described to associate with the Chlamydia inclusion, but a global picture of proteins contributing to the inclusion is currently missing
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