cAMP REGULATES PHAGOSOMAL MATURATION IN Staphylococcus aureus INFECTION.

GAURÓN, MC; COLOMBO, MI

Ciudad Autónoma de Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencia; 2017

SAIB

Staphylococcus aureus is a microorganism that causes serious diseases in humans, it is known that is able to induce an autophagic response in the host cell upon its infection. We have previously demonstrated that the virulence factor a-hemolysin (Hla) is the responsible of this autophagic response induced by S. aureus and it is used by the microorganism for escaping from its containing phagosome labelled with the autophagic protein LC3. We further demonstrated that the autophagic response induced by this bacterium is independent of the canonical PI3K/Beclin1 pathway and is instead regulated by an AMPc/EPAC/Rap2b pathway. In the current work we studied the implication of this pathway in the maduration of the S. aureus?s phagosome. We have found that the treatment of infected cells with the second messenger cAMP, besides of regulating the autophagic response induced by S. aureus, also regulates its phagosome maduration impairing it by the inhibition of the recruitment of the small GTPase Rab7. We further found that the cAMP analog, 8pCPT, which is able to specific activate Epac1, and the overexpression of YFP-Epac1 itself, have the same effect. But when we studied the target of Epac1, Rap2b, the recruitment of Rab7 wasn?t impaired. So we conclude that cAMP regulates the maduration of the phagosome of S. aureus in an Epac dependent, and Rap2b independent-manner.