Bacterial infections targeting the
bloodstream lead to a wide array of devastating diseases such as
septic shock and
meningitis. To study this crucial type of
infection, its specific environment needs to be taken into account, in particular the mechanical forces generated by the
blood flow. In a previous study using
Neisseria meningitidis as a model, we observed that
bacterial microcolonies forming on the
endothelial cell surface in the vessel lumen are remarkably resistant to mechanical stress. The present study aims to identify the molecular basis of this resistance.
N. meningitidis forms aggregates independently of
host cells, yet we demonstrate here that cohesive forces involved in these
bacterial aggregates are not sufficient to explain the stability of colonies on cell surfaces. Results imply that
host cell attributes enhance microcolony cohesion. Microcolonies on the cell surface induce a cellular response consisting of numerous cellular protrusions similar to
filopodia that come in close contact with all the
bacteria in the microcolony. Consistent with a role of this cellular response,
host cell lipid microdomain disruption simultaneously inhibited this response and rendered microcolonies sensitive to
blood flow-generated
drag forces. We then identified, by a
genetic approach, the type IV pili component PilV as a
triggering factor of
plasma membrane reorganization, and consistently found that microcolonies formed by a pilV
mutant are highly sensitive to shear stress. Our study shows that
bacteria manipulate
host cell functions to reorganize the
host cell surface to form filopodia-like structures that enhance the cohesion of the microcolonies and therefore
blood vessel colonization under the harsh conditions of the
bloodstream.
