Chlamydia trachomatis recruits and activates PKCδ and PKCε as survival strategy

CAPMANY A; GAMBARTE J; DAMIANI MT

Buenos Aires

Congreso; SAIB "Molecular Mechanims in cell signaling and gene expression; 2013

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

Chlamydia trachomatis is an obligate intracellular bacterium that replicates in a vacuole called inclusion and causes genital and ocular infections in humans. We have shown that C. trachomatis activates the Akt/AS160 pathway to ensure the arrival of Rab11- and Rab14-vesicles full of sphingolipids to the inclusion. Depending on cell type, PKCε activates or inactivates Akt, either by direct phosphorylation or by the action of a phosphatase. In addition, C. trachomatis recruits PKCδ as a protective mechanism against apoptosis. We postulate that C. trachomatis recruits both PKCδ and PKCε not only as a strategy to inhibit apoptosis, but also to ensure the arrival of Rab11- and Rab14-vesicles full of lipids. We transfected HeLa cells with different PKC isoforms (PKCβII, PKCα, PKCδ and PKCε and PKCζ), and we observed that only PKCδ and PKCε are recruited to the chlamydial inclusion. Infected cells were treated with several kinase inhibitors, like Rottlerin (PKCδ), Gö 6983 (PKCα) and H89 (PKA), and only Rottlerin completely inhibits the development of bacteria. Furthermore, treatment with Rottlerin or Calphostin (a general inhibitor of PKC) modifies the intracellular distribution of Rab14 and prevents its recruitment to the inclusion membrane. These data suggest that C. trachomatis could selectively activate both PKCδ and PKCε to ensure the arrival of nutrients and to guaranty its survival.