Coxiella burnetii modulates Beclin 1 and Bcl-2 preventing host cell apoptosis to generate a persistent bacterial infection.

VÁZQUEZ, CRISTINA L; COLOMBO, MARÍA I

CELL DEATH AND DIFFERENTIATION

Nature publishing group

Año: 2009

1350-9047

Coxiella burnetii is the etiological agent of the human disease Q fever and is anobligate intracellular bacterium that invades and multiplies in a vacuole with lysosomalcharacteristics. We have previously shown that Coxiella interacts with the autophagicpathway as a strategy for its survival and replication. In addition, recent studies haveshown that Coxiella exerts anti-apoptotic activity to maintain the host cell viability,generating a persistent infection. In the present report we have explored the role ofBeclin 1 and Bcl-2 in C. burnetii infection to elucidate how this bacterium modulatesautophagy and apoptosis to its own benefit. Beclin 1, a Bcl-2 interacting protein, isrequired for autophagy. We show here that Beclin 1 is recruited to the Coxiellamembranevacuole favoring its development and bacterial replication. In contrast, theanti-apoptotic protein Bcl-2 alters the normal development of the Coxiella-replicativecompartment, in spite of also being recruited to the vacuole membrane. Furthermore,both vacuole development and the anti-apoptotic effect of C. burnetii are affected byBeclin 1 depletion and by the expression of a Beclin 1 mutant defective in Bcl-2binding. Overall, these findings indicate that C. burnetii infection modulates autophagyand apoptotic pathways via Beclin 1/Bcl-2 interplay to establish a successful infectionin the host cell.