IHEM   20887
INSTITUTO DE HISTOLOGIA Y EMBRIOLOGIA DE MENDOZA DR. MARIO H. BURGOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
The toxin alfa-hemolysin is the factor responsible for the activation of the autophagic pathway in Staphylococcus aureus infected cells.
Autor/es:
MESTRE, B.; FADER, C.M.; COLOMBO, M.I.
Lugar:
Ortona, Italia.
Reunión:
Workshop; Lipid signaling and disease; 2009
Resumen:
The toxin a-hemolysin is the factor responsible for the activation of the autophagic pathway in Staphylococcus aureus infected cells Mestre MB, Fader CM and Colombo MI. IHEM-CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Casilla de Correo 56, 5500, Mendoza, Argentina. S. aureus induces a caspase-independent cell death, with the participation of autophagy. This pathway involves the sequestration of cytosolic components, organelles and microorganisms in a vacuole, the autophagosome, which finally fuses with the lysosome (1). Our purpose was to identify the factor(s) and the signaling mechanisms that participate in the activation of the autophagic response caused by S. aureus. a-Hemolysin is a pore forming toxin secreted by S. aureus(2,3 y 4). CHO cells over-expressing GFP-LC3 (an autophagosome marker) were incubated with the toxin. This caused a marked activation of autophagy in a concentration-dependent manner. In order to address if the toxin is the only secreted factor responsible for the activation of autophagy, CHO GFP-LC3 cells were   infected with the following S. aureus strains: wt, a mutant deficient for a-Hemolysin (Hla-) and the Hla(-) mutant expressing an a-Hemolysin plasmid. S. aureus wt as well as the mutant expressing the plasmid stimulated autophagy upon infection. In contrast, the Hla(-) mutant was unable of activating this pathway. In addition, we demonstrated that autophagy activation was calcium dependent, since this was hampered by the intracellular calcium chelator BAPTA-AM. Interestingly, the toxin effect was not prevented by the classical autophagy inhibitors 3-MA and Wortmannin, suggesting that the action of a-Hemolysin is independent of the Class III phosphatidylinositol 3-kinase, required for the autophagic pathway (5,6 y 7).