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Microvilli-like structures are associated with the internalization of virulent capsulated Neisseria meningitidis into vascular endothelial cells

¹ INSERM U411, Faculté de Médecine Necker-Enfants Malades, Université René Descartes, Paris, France
² CNRS UPR 415, Institut Cochin de Génétique Moléculaire, Paris, France

^* Author for correspondence (e-mail: nassif{at}necker.fr

Accepted 12 December 2001

Bacterial pathogens are internalized into non-phagocytic cells either by a zipper mechanism involving a direct contact between a bacterial ligand and a cellular receptor or a trigger mechanism secondary to the formation of membrane ruffles. Here we show that internalization of capsulated Neisseria meningitidis within endothelial cells following type IV pilus-mediated adhesion is associated with the formation of cellular protrusions at the site of bacterial attachment. These protrusions, like microvilli, are highly enriched in ezrin and moesin, two members of the ERM (ezrin/radixin/moesin) family, whereas vinculin and paxillin are absent. ERM-binding transmembrane proteins, such as CD44, and cortical actin polymerization colocalized within these membrane protrusions. Expression of dominant-negative ezrin largely prevented cortical actin polymerization, thus confirming the role of this molecule in bacteria-induced cytoskeletal modifications. Moreover, using selective inhibitors and dominant-negative mutants of the Rho family GTPases, we show that bacteria-induced actin polymerization required the activation of both Rho and Cdc42 but not of Rac1. Whereas GTPase inhibition dramatically reduced actin polymerization at the site of bacterial attachment, ezrin recruitment was not affected, indicating that bacterial adhesion promotes ezrin recruitment independently of the activity of the Rho-GTPases. Furthermore, GTPase inhibition largely reduced N. meningitidis entry into endothelial cells without affecting adhesion. We thus propose that following pilus-mediated adhesion, capsulated N. meningitidis recruit ERM-binding transmembrane proteins, as well as ezrin and moesin, and that both Rho and Cdc42 are critical for the subsequent cytoskeletal modifications responsible for the formation of microvilli-like cellular protrusions and bacterial internalization.

Key words: Neisseria, Ezrin, Microvilli, Meningitis

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