Biophysical Society Thematic Meeting | Ascona 2026

Mechanobiology of Infection

Poster Abstracts

26-POS Board 26 MENINGOCOCCAL TYPE IV PILI DRIVE LOCALIZED EXOCYTOSIS THROUGH HOST MEMBRANE REMODELING Kevin Sollier 1 ; Stefano Marullo 2 ; Mathieu Coureuil 3 ; Daria Bonazzi 1 ; 1 Institut Jacques Monod , CNRS UMR 7592, INSERM ERL 1340, Paris, France 2 Institut Cochin, Université Paris Cité, INSERM U1016, CNRS UMR8104, Paris, France 3 Institut Necker Enfants Malades (INEM), Université Paris Cité, INSERM U1151, CNRS UMR8253, Paris, France Neisseria meningitidis is a human-specific pathogen causing meningitis, representing a major public health burden. While it primarily colonizes the nasopharynx, it can occasionally breach epithelial barriers and enter the bloodstream, where it adheres to vascular endothelium under strong mechanical constraints and within a limited time window. Type IV pili (T4P) promote bacterial adhesion to endothelial cells by inducing tubular membrane structures (TMS) through one-dimensional wetting, a purely mechanical process independent of cellular signaling that drives host plasma membrane growth along bacterial pili. These TMS subsequently concentrate transmembrane proteins via an active host cellular response, through an as yet uncharacterized mechanism. Here, we seek to understand how T4P drive TMS formation through their impact on local host membrane organization, and whether membrane trafficking contributes to this process. FRAP analyses reveal a local decrease in transmembrane protein mobility in TMS, which extends to lipid dynamics, indicating reduced membrane fluidity. Membrane tension measurements further reveal a localized decrease in plasma membrane tension at sites of infection. This reduction suggests an increase in membrane area, potentially linked to membrane addition processes. In agreement with these observations, LAMP1-positive vesicles accumulate beneath bacterial colonies, while CD63-pHluorin imaging reveals localized fusion of late endosomal/lysosomal compartments with the plasma membrane. Inhibition of Golgi-dependent trafficking with Golgicide A significantly reduces TMS length, supporting a functional link between vesicular trafficking and bacterial-driven membrane remodeling. Together, these findings suggest that meningococci mechanically hijack host membrane organization through their T4P. Changes in membrane dynamics, including reduced lateral mobility, are observed, although their mechanistic origin remains to be determined. Membrane tension is also decreased and correlates with TMS formation, but their mechanistic interplay remains unclear. Ongoing work aims to determine whether these events involve membrane recycling and exocytic fusion pathways, as well as molecular regulators of plasma membrane addition.

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