Chlamydia trachomatis are Gram-negative bacteria that become endocytosed into host cells and spend their lives in vacuoles called inclusions. Although it is known that multivesicular bodies (MVBs) are a main source of cholesterol and sphingolipids required for Chlamydia trachomatis growth and replication, it is unclear how the bacteria coerce their host into delivering MVBs to the inclusion bodies. On page , Maria Teresa Damiani and colleagues now provide the first evidence that a late endocytic Rab GTPase is involved in chlamydial infection. They found Rab39a at MVBs and a specific subset of late endocytic vesicles, which dynamically associate with bacterial inclusions throughout the course of an infection. Interestingly, towards the later stages of infection, Rab39a-positive MVBs were also detected inside the inclusions. In addition, the authors showed that Rab39a recruitment to inclusions is initiated by bacterial proteins and requires an intact microtubule network, as well as that Rab39a needs to be in a GTP-bound state. Importantly, Rab39a overexpression increased the trafficking of MVBs and sphingolipids to the inclusions, whereas knockdown diminished it. Moreover, Rab39a knockdown resulted in Chlamydia forming smaller inclusions and generating fewer infectious particles. In conclusion, this study provides new insights into the biology of chlamydial infection by demonstrating that C. trachomatis hijack the Rab39a trafficking pathway to acquire sphingolipid-rich MVBs required for their growth and replication.
