Chlamydia trachomatis manipulates Akt/AS160/Rab14 pathway for sphingolipids acquisition from infected cells

DAMIANI MT; CAPMANY A.; LUJÁN A; ALONSO BIVOU M; CATANIA P; GAMBARTE TUDELA J

MERLO

Congreso; XXXV Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2017

SBCuyo

Chlamydia trachomatis (CT) is an obligate intracellular bacterium that replicates in a bacterialmodified phagosome called inclusion. By hijacking Rab functioning, CT exploits different trafficking pathways to acquire nutrients essential for its survival. We have demonstrated that Rab14 is recruited to the inclusion and drives sphingolipids delivery from the Golgi to the inclusion. In addition, Akt, a Serine/Threonine kinase, phosphorylates AS160 (Akt Substrate 160), a GAP (GTPase Activating Protein) for several Rab proteins, including Rab14. The phosphorylation of AS160 results in the inhibition of its GAP activity, thereby the Rabs remain associated to GTP, thus, in their active state. In this work, we demonstrate that CT, through the manipulation of theAkt/AS160 pathway, ensures the capture of Golgi-derived sphingolipids delivered by Rab14-positive vesicles. The blockage of Akt activation reduces not only Rab14 association with the inclusion but also decreases chlamydial inclusion size in a dose-dependent manner. Moreover, abnormal bacterial forms are likely produced during Akt inhibition. Likewise, bacterial multiplication and infectivity measured by inclusion forming unit analysis is clearly diminished byiAkt treatment and AS160 interference. These data suggest that CT selectively usurps Akt/AS160 pathway to ensure the delivery of sphingolipids necessary for its survival and development.