The Proteome of the Isolated <i>Chlamydia trachomatis</i> Containing Vacuole Reveals a Complex Trafficking Platform Enriched for Retromer Components

<div><p><i>Chlamydia trachomatis</i> 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 <i>Chlamydia</i> infections. Despite its importance for <i>Chlamydia</i> 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 <i>C</i>. <i>trachomatis</i> 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 <i>C</i>. <i>trachomatis</i> infection and that retrograde trafficking is essential for infectious progeny formation. In summary, these findings suggest that <i>C</i>. <i>trachomatis</i> hijacks retrograde pathways for effective infection.</p>