title: Early sequence of events triggered by the interaction of Neisseria meningitidis with endothelial cells.
abstract: Neisseria meningitidis is a bacterium responsible for severe sepsis and meningitis. Following type IV pilus-mediated adhesion to endothelial cells, bacteria proliferating on the cellular surface trigger a potent cellular response that enhances the ability of adhering bacteria to resist the mechanical forces generated by the blood flow. This response is characterized by the formation of numerous 100 nm wide membrane protrusions morphologically related to filopodia. Here, a high-resolution quantitative live-cell fluorescence microscopy procedure was designed and used to study this process. A farnesylated plasma membrane marker was first detected only a few seconds after bacterial contact, rapidly followed by actin cytoskeleton reorganization and bulk cytoplasm accumulation. The bacterial type IV pili-associated minor pilin PilV is necessary for the initiation of this cascade. Plasma membrane composition is a key factor as cholesterol depletion with methyl-β-cyclodextrin completely blocks the initiation of the cellular response. In contrast membrane deformation does not require the actin cytoskeleton. Strikingly, plasma membrane remodelling undermicrocolonies is also independent of common intracellular signalling pathways as cellular ATP depletion is not inhibitory. This study shows that bacteria-induced plasma membrane reorganization is a rapid event driven by a direct cross-talk between type IV pili and the plasma membrane rather than by the activation of an intracellular signalling pathway that would lead to actin remodelling.
authors: Université Paris Descartes, Faculté de Médecine Paris Descartes, Paris, F-75006, France; INSERM, U970, Paris Cardiovascular Research Center, Paris, F-75015, France.
authors: Magali
authors: M
authors: Soyer
authors: Arthur
authors: A
authors: Charles-Orszag
authors: Thibault
authors: T
authors: Lagache
authors: Silke
authors: S
authors: Machata
authors: Anne-Flore
authors: AF
authors: Imhaus
authors: Audrey
authors: A
authors: Dumont
authors: Corinne
authors: C
authors: Millien
authors: Jean-Christophe
authors: JC
authors: Olivo-Marin
authors: Guillaume
authors: G
authors: Duménil
mesh_terms: D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D022081:Cell Surface Extensions / Q000378:metabolism / Q000382:microbiology; D042783:Endothelial Cells / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D008856:Microscopy, Fluorescence; D009345:Neisseria meningitidis / Q000502:physiology*; D061848:Optical Imaging; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors