Bacterial alginate regulators and phage homologs repress CRISPR-Cas immunity

CRISPR-Cas systems are adaptive immune systems that protect bacteria from bacteriophage (phage) infection(1). To provide immunity, RNA-guided protein surveillance complexes recognize foreign nucleic acids, triggering their destruction by Cas nucleases(2). While the essential requirements for immune activity are well understood, the physiological cues that regulate CRISPR-Cas expression are not. Here, a forward genetic screen identifies a two-component system (KinB/AlgB), previously characterized in regulating Pseudomonas aeruginosa alginate biosynthesis(3,4), as a regulator of the expression and activity of the P. aeruginosa Type I-F CRISPR-Cas system. Downstream of KinB/AlgB, activators of alginate production AlgU (a σ(E) orthologue) and AlgR, repress CRISPR-Cas activity during planktonic and surface-associated growth(5). AmrZ, another alginate regulator(6), is triggered to repress CRISPR-Cas immunity during surface-association. Pseudomonas phages and plasmids have taken advantage of this regulatory scheme, and carry hijacked homologs of AmrZ that repress CRISPR-Cas expression and activity. This suggests that while CRISPR-Cas regulation may be important to limit self-toxicity, endogenous repressive pathways represent a vulnerability for parasite manipulation.