Mechanical forces in bacterial pathogenesis: Sensing, tropism, and intervention.

Bacterial pathogenesis unfolds within mechanically complex host niches, yet physical forces are frequently overlooked as active drivers of virulence. Here, we argue that mechanical cues-shear, confinement, and matrix rheology-serve as essential regulatory inputs that dynamically reprogram bacterial physiology. We propose a multi-scale framework connecting force-dependent receptor kinetics and envelope-stress signaling to community-level biofilm viscoelasticity. This synthesis elucidates how bacteria interpret the specific force landscapes of human tissues, providing a mechanistic rationale for tissue-tropism that biochemical models alone cannot resolve. Finally, we posit that the "physicality" of infection presents an unexploited therapeutic frontier. By outlining strategies to target mechanotransduction nodes or exploit biofilm mechanical fragilities, we demonstrate how mechanics-based interventions offer orthogonal strategies to bypass antimicrobial resistance, shifting the paradigm from chemical inhibition to physical disruption.