Modulation and utilization of host cell phosphoinositides by Salmonella spp

The importance of phosphoinositides in cell biology has only been recognized in the last decade, largely because of the difficulty of working with these molecules. This difficulty has, to some extent, recently been overcome by the development of new technologies. We now know that phospholipids and their metabolites affect almost every process in the eukaryotic cell, and the mechanisms involved in these processes are gradually being elucidated. It is clear that Salmonella is also able to modulate the levels of phosphoinositides, both at the plasma membrane and on the SCV. The significance of this cannot be overemphasized since it provides the pathogen with numerous mechanisms to modulate essential host cell processes, including actin remodeling, signal transduction, and membrane trafficking. Unfortunately, at this point there are more questions than answers. For example, what is the function of Akt activation by SigD? Recent data from our laboratory suggest that this process may prevent or delay apoptosis in infected epithelial cells (Knodler and Steele-Mortimer, unpublished observations). What is clear, as we begin to identify the multiple mechanisms by which Salmonella interacts with host cells, is that this remarkable interplay presents us with unique opportunities to decipher complex eukaryotic pathways.