INVESTIGADORES
LEIVA Natalia Lorena
congresos y reuniones científicas
Título:
Rab14/Akt pathway is usurped by Chlamydia trachomatis to ensure its development
Autor/es:
CAPMANY A; LEIVA N; GAMBARTE J; DAMIANI MT
Lugar:
1-4 de septiembre de 2012, Costa Ballena, España y 4-9 de Septiembre, 2012, Sevilla, España
Reunión:
Congreso; Young Sientist Program . 22nd IUBMB and 37 th FEBS Congress; 2012
Institución organizadora:
IUBMB & FEBS
Resumen:
Chlamydia trachomatis, an obligate intracellular pathogen, is the most frequent sexually-transmitted bacterial disease worldwide. Chronic infections can result in female infertility. These bacteria exploit different trafficking pathways to acquire nutrients essential for their survival. We have demonstrated 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 the Golgi to the inclusion. Furthermore, we have recently observed that infection with C. trachomatis causes an increase in the expression of host Rab14. On the other hand, it has been described that Akt, a Ser/Thr kinase, phosphorylates AS160, a GAP (GTPase Activating Protein) for Rab14. The phosphorylation of AS160 results in the inhibition of its GAP activity, leaving Rab14 in its active state bound to GTP. We postulate that C. trachomatis might manipulate PI3K/Akt pathway to ensure the arrival of sphingolipids delivered from the Golgi to the inclusion through Rab14-positive vesicles. We analyzed the effect of a specific AKT inhibitor (iAkt) on HeLa cells infected with C. trachomatis. Treatment with iAkt decreased chlamydial inclusion size, inhibited homotypic fusion and reduced Rab14 recruitment to the inclusion in a doses-dependent manner. Moreover, iAKT treatment of infected cells provoked the retention of sphingolipids within the Golgi apparatus and generated abnormal bacterial forms observed by electron microscopy. Coincidently, these aberrant bacteria, typical of persistent infections, were likely observed within sphingomyelin-deficient cells. Likewise inclusion forming unit analysis clearly showed that iAKT treatment significantly decreased bacterial multiplication and infectivity. These data suggest that Chlamydia trachomatis selectively usurps PI3K/Akt pathway to generate an intracellular niche favourable for its survival.