IHEM   20887
Unidad Ejecutora - UE
congresos y reuniones científicas
33. Mycobacterium and Staphylococcus aureus: autophagic response in infected cells
Mar del Plata, Argentina
Congreso; SAIC; 2009
    ABSTRACT CONFERENCIA SAIC 2009   Mycobacterium and Staphylococcus aureus: autophagic response in infected cells. María Isabel Colombo- IHEM-CONICET- Fac. de Cs. Médicas- U. N. de Cuyo-Mendoza-Argentina Numerous pathogens invade host cells to be protected from immunity, but once in the host cell they use sophisticated strategies to avoid destruction. Cumulative evidence indicates that autophagy is one of the most remarkable tools of the intracellular host cell defense machinery that bacteria must confront upon invasion. However, several pathogens subvert the autophagic pathway and, manipulate this process as a strategy to establish a persistent infection. Mycobacterium tuberculosis is a facultative intracellular pathogen that colonizes and multiplies in host macrophages. The success of Mycobacterium relays on its ability to modulate the intracellular environment. After internalization M. tuberculosis is capable of persisting within the phagosomal compartment, interfering with the typical phagosomal maturation process. We have demonstrated that induction of autophagy leads to acidification and maturation of the M. tuberculosis phagosome, with a concomitant decrease in the intracellular survival of the bacilli. In addition, our results indicate that IFN-g activated autophagy participates in the innate immune response for the eradication of M. tuberculosis, establishing a key relationship between immune mediators and protection against intracellular pathogens. Staphylococcus aureus is a pathogen that causes serious infectious diseases eventually leading to septic and toxic shock. Classically S. aureus has been considered an extracellular pathogen, but cumulative evidence indicates that it invades cells and replicates intracellularly, leading to staphylococcal persistence and chronic disease. This pathogen initially localizes to autophagic compartments but inhibits their maturation and fusion with lysosomes, thus S. aureus avoids the normal autophagosomal pathway toward degradative compartments.  One of the key features of S. aureus infection is the production of a series of virulence factors, including secreted enzymes and toxins. Our results indicate that the pore-forming toxin Hla is the S. aureus secreted factor responsible for the activation of the autophagic pathway. Early after infection S. aureus disrupts the pathogen-containing vacuole membrane to escape towards the cytoplasm where actively replicates. Interestingly, S. aureus is not able to replicate in autophagy-deficient atg5-/- MEFs, indicating that this pathogen takes advantage of the host cell autophagy for a successful colonization.