Plasma membrane remodeling by Neisseria meningitidis is driven by a wetting process along type IV pili fibers

Abstract

Neisseria meningitidis is a bacterial pathogen that colonizes human blood vessels and causes septic shock and meningitis. Adhesion of meningococci to host endothelial cells via type IV pili is accompanied by a potent remodeling of the host cell plasma membrane, forming filopodia-like protrusions that intercalate between aggregated bacteria. While the mechanism behind plasma membrane remodeling remains unknown, the plasma membrane protrusions have been shown to increase microcolony resistance to shear stress. Here we first show that plasma membrane remodeling takes place during bacterial colonization of human blood vessels in vivo. In vitro, we find that remodeling occurs at the level of the single adhering bacterium as discrete short-lived protrusions, which then stabilize in between aggregated bacteria in the microcolony. Cortical actin polymerization is not necessary for protrusion formation but stabilizes them. Several observations point to a scaffolding mechanism exerted by type IV pili. First, plasma membrane protrusions disappear upon pilus retraction. Second, electron microscopy shows that membrane protrusions grow alongside type IV pili fibers. Third, perturbing the architecture of the type IV pili meshwork hinders plasma membrane remodeling. Accordingly, we show that wetting onto adhesive nanofibers can drive tubulation of phospholipid vesicles, and that the plasma membrane of human endothelial cells deforms locally in response to adhesive nanotopographical cues. Therefore, we propose that the human endothelial cell plasma membrane deforms onto type IV pili fibers through a linear wetting mechanism which reflects a general property of biological membranes in contact with adhesive nanofibrillar structures.