Staphylococcus aureus alpha-Toxin Activates MAPKS and Alters c-Jun and KLF6 Protein Levels in Lung Cells.

MOYANO, ALEJANDRO J.; ANDREOLI, VERÓNICA; RACCA, ANA C.; SOLA, CLAUDIA; PANZETTA-DUTARI, GRACIELA; BOCCO, JOSÉ L.

Potrero de Los Funes. San Luis

Congreso; XLVII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2011

SAIB

The Staphylococcus aureus a-toxin is a key virulence factor involved in the onset of diverse and often fatal infections, such us necrotizing pneumonia. However, its molecular mechanisms are not well understood. The biochemical response mediated by the main group of Mitogen-Activated-Protein Kinases (MAPKs) JNK, p38 and ERK in A549 lung epithelial cells intoxicated with a-toxin was analyzed. Distribution of c-Jun and KLF6 transcription factors, which are key regulators of cell fate upon diverse stimuli, including microbial infections was additionally investigated. Western-Blot (WB) analyses of cells treated with S. aureus culture supernatants or with purified a-toxin, showed the activation of the three MAPKs ? JNK, p38 and ERK ? phenomenon which was not observed in cells treated with supernatants from an isogenic a-toxin-deficient srain. Pharmacological inhibition of MAPKs indicates that activation of the three pathways were important for cell survival. Furthermore, atoxin increase phosphorylation and decreased the c-Jun protein level. Finally, WB of nuclear and cytoplasmic fractions, as well as confocal microscopy, showed that a-toxin provoked a fast decrease of KLF6 at the nucleus, while gaining a more cytoplasmic distribution. These results shed light on the role MAPKs pathways and the involvement of c-Jun and KLF6 in the complex cell response upon S. aureus a-toxin intoxication.