Mechanobiological mechanisms of bacterial infection-host defense interactions

Summary Recent advances in infection biology have increasingly underscored that mechanical forces and microenvironmental cues shape host-pathogen interactions in critical, stage-specific manners. Key mechanical inputs—such as fluid shear stress, cortical tension, and extracellular matrix (ECM) stiffness—can markedly modulate bacterial adhesion to host cells, subsequent invasion, and dissemination. In this review, we propose a mechano-regulatory framework in which infection and host defense co-evolve through a bidirectional "mechanical tug-of-war." Within this framework, mechanical cues tune bacterial behaviors, while host tissues mount mechanically driven defenses, including epithelial extrusion, to remove infected cells. We further highlight emerging anti-infective opportunities that target mechanical vulnerabilities, ranging from force-stabilized adhesion inhibitors to engineered, mechanically gated therapeutics and stiffness-tailored implants. By integrating mechanobiology, mechanomedicine, and microbiology, this growing field may enable more targeted and effective therapies for bacterial infections.