CRISPR-Cas Systems: Bridging Bacterial Immunity and Host Interactions

CRISPR-Cas systems are best known as adaptive immune defenses in prokaryotes, but they also function as versatile regulators bridging bacterial immunity with host-related processes. Beyond neutralizing invasive phages and plasmids, these systems influence core aspects of bacterial physiology, such as modulating gene expression, stress responses, biofilm formation, quorum sensing, and virulence. Notably, CRISPR-mediated regulation can facilitate immune evasion at the host-pathogen interface, underscoring these systems as central orchestrators of microbial survival and host interactions. In addition, CRISPR-Cas has rapidly become a cornerstone of synthetic biology and microbiome engineering. Recent strategies repurpose native and engineered CRISPR systems to precisely modulate microbiome composition or deliver sequence-specific antimicrobials, underscoring the expanding translational potential of this system. Collectively, emerging insights highlight both the canonical immune function and non-canonical regulatory roles of CRISPR-Cas, as well as their broad biological and biotechnological relevance. This review provides a critical synthesis of these developments, illustrating how CRISPR-Cas bridges adaptive immunity and microbial physiology, and outlines future directions for harnessing this duality to deepen understanding of microbial physiology and inform new translational applications.