Chlamydia trachomatis USURPS HOST Akt KINASE NETWORK FOR ITS BENEFIT

CAPMANY A; LEIVA N; DAMIANI MT

Puerto Madrin, Chubut

Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2010

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Chlamydia trachomatis, an obligate intracellular pathogen, is the most frequent sexually-transmitted bacterial disease worldwide. This bacterium usurps host cell components to generate its intracellular replicative vacuole called inclusion. Chlamydial inclusion diverts from the endocytic pathway but interacts with the biosynthetic/exocytic via. Different host cell lipids including sphingolipids are essential for Chlamydia development. We have shown that Rab14, a key regulator of vesicular transport between the Golgi apparatus and early endosomes, is recruited to the inclusion and is involved on sphingolipids delivery from Golgi to the inclusion. On the other hand, it has been described that AKT, a Ser/Thr kinase, phosphorylates AS160, a GAP (GTPase Activating Protein) of Rab14. The phosphorylation of AS160 results in the inhibition of its GAP activity, leaving Rab14 in its active state bound to GTP. We analyzed the effect of specific AKT inhibitors in HeLa cells overexpressing GFP-Rab14wt infected with C. trachomatis. AKT inhibitors decreased chlamydial inclusion size and bacterial multiplication. Furthermore, Rab14 was not recruited to the inclusion and the transport of sphingolipids from the Golgi to the inclusion was significantly diminished. These results suggest that Chlamydia trachomatis selectively uses AKT pathway to activate Rab14-mediated sphingolipid transport