MODULATION OF HOST ACTIN CYTOSKELETON BY THE LEGIONELLA EFFECTOR RAVJ

The actin cytoskeleton is involved in many essential cellular events such as mitosis, cell migration, control of epithelial barrier function, and adherence of immune cells. Given the essential roles of the actin cytoskeleton, it is not surprising that it is a common target for bacterial virulence factors. Legionella pneumophila, the causative agent of Legionnaire’s pneumonia, establishes a replicative compartment using effectors secreted by its Dot/Icm secretion system. At least four Dot/Icm effectors, VipA, Ceg14, LegK2 and RavK have been shown to modulate the host actin cytoskeleton. Here, we identified RavJ (lpg0944) as an additional effector that interferes with the actin cytoskeleton in mammalian cells. We demonstrated that RavJ is a transglutaminase that functions to induce crosslink between actin and members of the Motin protein family, leading to inhibition of the binding between actin and ADF/cofilin. We also found that LegL1 (lpg0945) is a metaeffector of RavJ, which suppresses the transglutaminase activity of RavJ by blocking its enzymatic domain.