Role of Src family of tyrosine kinases in Pseudomonas aeruginosa infection of epithelial cells

PAOLA LEPANTO; ARLINET KIERBEL

Congreso; XLV Reunión Anual SAIB; 2009

Pseudomonas aeruginosa (PA) is an opportunistic pathogen that can cause urinary and respiratory acute infections as well as pulmonary damage and consequent death in patients with cystic fibrosis. More than half of clinical isolates can get internalized into non-phagocytic cells. This suggests an important role of internalization in PA infection. We approached the internalization mechanism using a model of epithelial cells (MDCK), infected by a human isolate of PA. We have shown that PA aggregates are found at MDCK apical surface associated to large host membrane protrusions. After longer infection periods, bacterial aggregates can be seen inside epithelial cells. We have also shown that the PI3K/AKT pathway is important for both protrusion formation and internalization. It has been reported that PI3K is regulated by tyrosine kinases and that PA infection induces a raise of host tyrosine phosphorylation. In the present work we address the role of Src family of tyrosine kinases (SFKs) in PA epithelial cell infection. Our results show that SFKs strongly activates upon PA infection. Inhibition of SFKs diminishes PA internalization while it partially reduces PI3K/AKT activation. Moreover, it profoundly alters protrusion formation. These findings point to an important role of SFKs in PA infection. Current work is aimed at the identification of the SFKs members involved in this process.