Mechanotransduction in bacteria: how Pseudomonas aeruginosa actively probes and responds to substrate mechanics

A growing body of evidence suggests that bacteria respond to mechanical cues such as shear flow or surface material properties, yet clear evidence that such mechanical features of the environment are integrated in a cell’s active decision making is lacking. Here, we demonstrate that the pathogen Pseudomonas aeruginosa employs arm-like, retractable appendages called pili to actively deform a substrate and probe its mechanical properties. We use a transcriptional fluorescence reporter to show that Pseudomonas tunes the expression of virulence factors based on substrate stiffness in the range of 0.1 – 1000 kPa. Using optical tweezers, traction force microscopy, and molecular modeling of the active motor components, we probe the mechanism of pilus-based mechanosensation. These results provide unique insights into the molecular functioning and control of pilus extension and retraction and how this is linked to twitching motility. We find evidence of an active bacterial mechanotransduction pathway that connects substrate mechanical properties to a genetic response via active surface deformation, similar to the mechanogenetic regulation found in stem cell differentiation.