Membrane-dependent actin polymerization mediated by the Legionella pneumophila effector protein MavH

Author summaryLegionella pneumophila, a bacterium discovered in 1976, can cause a severe lung infection known as Legionnaires' disease. Upon inhalation of contaminated aerosol, L. pneumophila releases over 330 bacterial proteins to facilitate its intracellular survival and proliferation. These secreted bacterial proteins target a variety of host cellular pathways, including the actin cytoskeleton. In this study, we focused on one of such secreted L. pneumophila proteins, called MavH. We found that MavH promotes actin assembly both in vitro and in vivo on the membrane surface and actin polymerization triggered by MavH further drives the deformation and tubulation of the membrane. Moreover, we found that MavH promotes the entry of the bacterium into host cells by regulating host actin dynamics. In summary, we identified MavH as a novel actin regulator that induces actin polymerization-dependent membrane tubulation and enhances the ability of L. pneumophila to infect its host. L. pneumophila propagates in eukaryotic cells within a specialized niche, the Legionella-containing vacuole (LCV). The infection process is controlled by over 330 effector proteins delivered through the type IV secretion system. In this study, we report that the Legionella MavH effector localizes to endosomes and remodels host actin cytoskeleton in a phosphatidylinositol 3-phosphate (PI(3)P) dependent manner when ectopically expressed. We show that MavH recruits host actin capping protein (CP) and actin to the endosome via its CP-interacting (CPI) motif and WH2-like actin-binding domain, respectively. In vitro assays revealed that MavH stimulates actin assembly on PI(3)P-containing liposomes causing their tubulation. In addition, the recruitment of CP by MavH negatively regulates F-actin density at the membrane. We further show that, in L. pneumophila-infected cells, MavH appears around the LCV at the very early stage of infection and facilitates bacterium entry into the host. Together, our results reveal a novel mechanism of membrane tubulation induced by membrane-dependent actin polymerization catalyzed by MavH that contributes to the early stage of L. pneumophila infection by regulating host actin dynamics.