Role of the small GTPase Rab39a in the course of the chlamydial infections

GAMBARTE TUDELA JULIAN; CAPMANY ANAHÍ; GOUD BRUNO; DAMIANI MT

Pornichet

Congreso; 17th annual meeting-Club exocytose-endocytose; 2014

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 alternate between two functional and morphological distinct forms. The metabolically inactive extracellular forms are termed elementary bodies (EBs), and the replicating, but noninfectious, forms are called reticular bodies (RBs). During its development, the 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 essential host-deriveved nutrients 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 manipulates Rab39-mediated vesicular trafficking. We defined Rab39a localization 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. Overexpression of GFP-Rab39a WT and its positive mutant (GFP-Rab39a Q72L) increases the chlamydial inclusion size and bacterial multiplication. Our results demonstrate 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 treatments with drugs that prevent the acidification of vesicles alter Rab39a recruitment to the inclusions and injure bacterial development. Furthermore, silencing of Rab39a by siRNA reduces bacterial multiplication and infectivity, assessed by the counting of inclusion forming units. Likewise, Rab39a silencing significantly decreases lipid acquisition from infected host cells by these bacteria. These data suggest that Chlamydia trachomatis selectively usurps Rab39a pathway to acquire essential lipids for its development, growth and replication.