Role of the small GTPase Rab39a in the course of Chlamidial infection

GAMBARTE J; CAPMANY A; GOUD B; DAMIANI MT

Pornichet, Ker Juliette

Workshop; 17 th annual meeting Club Exocytose -Endocytose; 2014

Club Exocytose-Endocytose

Chlamydia trachomatis is a Gram-negative obligate intracellular bacterium responsible of several significant human diseases, including blinding trachoma, urogenital tract infections and systemic lymphogranuloma venereo. This bacterium displays a unique developmental cycle that alternates between two functional and morphological distinct forms. The metabolically inactive extracellular form termed elementary body (EB), and the non-infectious replicating form called reticular body (RB). During its development, this bacterium resides and multiplies in a modified vacuole, not acidic, not degradative called inclusion. This pathogen establishes a complex set of interactions with host cell trafficking pathways to facilitate acquisition of host-derived molecules, essential for its survival. Rab proteins comprise a family of GTPases that controls eukaryotic cell traffic. The aim of this study was to investigate if Chlamydia trachomatis manipulates Rab39a-mediated vesicular trafficking. We defined the localization of Rab39a in multivesicular bodies, late endosomes and a subset of acidic vesicles. By confocal microscopy, we observed that Rab39a associates with the chlamydial inclusion throughout its development. In addition, our results demonstrated that Rab39a decorates vesicles carrying lysobisphosphatidic acid and sphingolipids, and plays a role in the delivery of these molecules from host multivesicular bodies to the chlamydial inclusion. Moreover, the treatment with drugs that prevent the acidification of vesicles altered Rab39a recruitment to the inclusions and impaired bacterial development. Overexpression of GFP-Rab39a WT and its positive mutant (GFP-Rab39a Q72L) increased the chlamydial inclusion size and bacterial multiplication. In agreement, silencing of Rab39a by siRNA reduced bacterial replication and infectivity, assessed by the counting of inclusion forming units. Likewise, Rab39a silencing significantly decreased lipid acquisition from infected host cells by these bacteria. These data suggest that Chlamydia trachomatis selectively usurps the Rab39a pathway to acquire essential lipids for its development, growth and replication.