Ultrasound-activatable bacteria for biomedical applications

Abstract

Bacteria have emerged as powerful therapeutic vectors owing to their intrinsic tumour tropism, genetic programmability, and living therapeutic functions. However, the trade-off between their autonomous proliferation and potential immunotoxicity restricts their clinical translation. Integrating ultrasound (US), a non-invasive physical trigger providing deep tissue penetration and high spatiotemporal precision, presents a potential solution to this dilemma. Acoustic actuation can safely bridge this gap by confining bacterial activity to pathological sites, thereby expanding the therapeutic window. Here, we summarize the fundamental biological mechanisms underlying US-bacteria interactions, including mechanical, thermal, and chemical effects. Building upon these principles, we detail emerging engineering strategies that confer US responsiveness to bacteria, such as surface functionalization, gas vesicle engineering, and sonogenetic regulation. Subsequently, we highlight recent advances in US-responsive bacterial systems across diverse applications, including biomedical imaging, targeted drug delivery, and microenvironment reprogramming. Finally, we discuss the key challenges that hinder clinical translation and propose future research directions. Overall, this review highlights the significant potential of integrating engineered bacteria with US technologies and provides a roadmap for next-generation precision diagnostics and therapeutics.