Mechanisms and Pathological Significance of Liquid–Liquid Phase Separation in Bacteria

Abstract

Liquid–liquid phase separation (LLPS) has emerged as a fundamental regulatory mechanism in bacterial physiology, orchestrating essential cellular processes including gene expression, stress responses, metabolic homeostasis, and biofilm formation. This phenomenon is driven by intrinsically disordered regions (IDRs), multivalent interactions between modular domains, and dynamic protein-nucleic acid associations, with precise modulation by environmental parameters such as temperature, ionic strength, and post-translational modifications (PTMs). The resulting functional condensates confer enhanced environmental adaptability and contribute to antibiotic resistance mechanisms in bacterial populations. These assemblies further impact host-pathogen interactions through modulation of virulence factor expression and immune evasion strategies, thereby complicating infection management. This comprehensive review systematically examines the molecular mechanisms driving LLPS, its dynamic regulatory networks, and physiological functions in bacteria. We evaluate the therapeutic potential of targeting LLPS pathways for antimicrobial development, with particular emphasis on antibiotic resistance regulation and intestinal commensal colonization. Future research should elucidate the mechanistic roles of LLPS-associated biomacromolecules in bacterial physiology, characterize their assembly and disassembly dynamics, and explore their therapeutic applications to establish a theoretical foundation for innovative antimicrobial strategies.