Phosphoinositides play a central role in the control of several cellular events including actin cytoskeleton organization.Here we show that, upon infection of epithelial cells with the Gram-negative pathogen Shigella exneri, the virulence factor IpgD is translocated directly into eukaryotic cells and acts as a potent inositol 4-phosphatase that specically dephosphorylates phosphatidylinositol 4,5-bisphosphate [PtdIns-(4,5)P 2 ] into phosphatidylinositol 5-monophosphate [PtdIns(5)P] that then accumulates.Transfection experiments indicate that the transformation of PtdIns(4,5)P 2 into PtdIns(5)P by IpgD is responsible for dramatic morphological changes of the host cell, leading to a decrease in membrane tether force associated with membrane blebbing and actin lament remodelling.These data provide the molecular basis for a new mechanism employed by a pathogenic bacterium to promote membrane rufing at the entry site.