Apical adhesion of extracellular bacteria modulates host cell mechanics through a novel actomyosin structure

Pathogenic bacteria have various strategies to invade the host, including the hijacking of host cell components such as cell membrane, cytoskeleton, cell-cell junction, and/or cell-ECM adhesion molecules to mediate bacterial adhesion, proliferation, and dissemination. Recent studies have proposed that these processes also involve major changes in host cell mechanics; however, the forces bacteria generate or induce in the host and their functional impact on tissue physiology and tissue integrity remain largely unexplored, especially in the case of extracellular pathogens. To address this question, we investigate how Neisseria meningitidis (Nm) modulates endothelial cell mechanics upon adhesion, and its potential relationship with key pathological signatures of this infection, e.g. vascular damage. Previous work has shown that Nm binding on the host cell membrane (apical surface) induces major remodeling of the plasma membrane and actin cortex. This is mediated by type-IV pili and leads to the formation of a honeycomb-like structure at the infection site termed cortical plaque, with thin protrusions intercalating between bacteria. This has been shown to be important for bacterial resistance to blood flow-generated shear stress, however, its impact on global host cell mechanics is unknown. Here, we found for the first time that the cortical plaque is not limite to the apical cell membrane, but it extends to the basal cell membrane. These columnar extensions are actin-rich, and we term them “Ancreopodia”. We bring to light that Ancreopodia assist the extracellular bacteria to sense the basal extracellular matrix (ECM), establish strong anchoring, and transmit forces.This mechanical control over the host cell could directly impact infection progression, by favoring barrier crossing and vascular damage.