How mechanical forces shape bacterial infections?

Mammalian cells sense and exert forces on their environment, and their responses to mechanical signals regulate their growth, motility, and behavior within tissues. However, little is known about the forces at play during microbial infections, and their impact on tissue homeostasis and disease progression. 
On the bacterial side, we investigated how mechanical constraints imposed upon confinement affect bacterial physiology using a microfluidic device ensuring nutrient access. In E. coli, we found that cells generate growth-induced pressure in the hundreds of kPa range decoupling growth and division, producing shorter bacteria due to increased cytoplasmic protein concentrations and crowding. Despite decreased protein synthesis, theoretical modeling predicts a novel regime of steady pressure increase, termed overpressurization, leading to transcriptional adaptation of the bacterial cell envelope to maintain cell shape. Finally, we highlight the relevance of these pressurized regimes during infection of uropathogenic E. coli and other bacterial pathogens.
On the host side, we recently found that binding of the extracellular bacterium Neisseria meningitidis (Nm) on the endothelium leads to the generation of large traction forces on the extracellular matrix. This is due to the formation of a new actin-rich structure, that we called ancreopodia, linking the bacterial colony on the apical side of the host cell to the basal side and underlying substrate. Using super-resolution microscopy, we identified distinct apical, middle, and basal domains of ancreopodia, which significantly reorganize basal actin stress fibers, induce focal adhesions, and increase local traction forces. Dynamic imaging showed synchronized movements between bacterial colonies and basal mechanosensitive proteins, indicating direct mechanotransduction from apical infection sites to the extracellular matrix (ECM). Preliminary data suggest ancreopodia cause topological defects in basal actin networks, potentially inducing long-range force transmission throughout the infected cells, leading to alterations in tissue function. In the next future, we propose to dissect how host cell mechanics is affected by Nm infection, and how mechanical forces globally impact tissue barrier physiology in epithelia and endothelia. This will bring new fundamental knowledge on the mechanical homeostasis of tissue barriers, by integrating extracellular pathogens as new tools to shed light on complex feedbacks between cell architecture, mechanics, and function.