Chlamydia trachomatis intercepts Golgi-derived sphingolipids through a Rab14-mediated transport required for bacterial development and replication.
Chlamydia trachomatis are obligate intracellular bacteria that survive and replicate in a bacterial-modified phagosome called inclusion. As other intracellular parasites, these bacteria subvert the phagocytic pathway to avoid degradation in phagolysosomes and exploit trafficking pathways to acquire both energy and nutrients essential for their survival. Rabs are host proteins that control intracellular vesicular trafficking. Rab14, a Golgi-related Rab, controls Golgi to endosomes transport. Since Chlamydia establish a close relationship with the Golgi apparatus, the recruitment and participation of Rab14 on inclusion development and bacteria growth were analyzed. Time course analysis revealed that Rab14 associated with inclusions by 10 h post infection and was maintained throughout the entire developmental cycle. The recruitment was bacterial protein synthesis-dependent but independent of microtubules and Golgi integrity. Overexpression of Rab14 dominant negative mutants delayed inclusion enlargement, and impaired bacteria replication as determined by IFU. Silencing of Rab14 by siRNA also decreased bacteria multiplication and infectivity. By electron microscopy, aberrant bacteria were observed in cells overexpressing the cytosolic negative Rab14 mutant. Our results showed that Rab14 facilitates the delivery of sphingolipids required for bacterial development and replication from the Golgi to chlamydial inclusions. Novel anti-chlamydial therapies could be developed based on the knowledge of how bacteria subvert host vesicular transport events through Rabs manipulation.
Cell Biology Laboratory, Biochemistry Department, IHEM-CONICET, Faculty of Medicine, University of Cuyo, Mendoza, Argentina.
Anahí
A
Capmany
María Teresa
MT
Damiani
D001426:Bacterial Proteins / Q000378:metabolism; D001692:Biological Transport; D002692:Chlamydia trachomatis / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000648:ultrastructure; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D034622:RNA Interference; D013107:Sphingolipids / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D013107:Sphingolipids; D049452:Green Fluorescent Proteins; C553411:Rab14 protein, human; D020691:rab GTP-Binding Proteins