By using a variety of multidisciplinary methods such as bacterial genetics, cell biology and biochemistry, our studies focus on the mechanisms of how L. pneumophila modulates two cellular processes to promote its intracellular growth. The first is the apoptotic pathways. Our study showed that the bacterium inhibits apoptosis of host cells by interacting with pro- death members of the Bcl2 protein family. The second line of research in this direction is the identification of bacterial factors responsible for the induction of host anti-apoptotic genes. On the other hand, we have identified several bacterial proteins that exert toxic effects to host cells and we are characterizing the biochemical mechanisms underlying such toxicity.
The second focus of our study is the mechanisms of the biogenesis of bacterial vacuoles, particularly those underlying the recruitment of membrane materials from the endoplasmic reticulum (ER) and the inhibition of phagosome acidification by the bacterium. Our recent progress indicated that the Dot/Icm transporter substrate SidJ is required for efficient recruitment of ER proteins to the bacterial phagosome. The current goals are the elucidation of the biochemical activity of this protein and how it coordinates with other effectors to recruit ER materials.