Bacterial alginate regulators and phage homologs repress CRISPR-Cas immunity

The identification of the KinB-AlgB two-component system, known to modulate alginate biosynthesis, together with downstream proteins that repress the Type I-F CRISPR-Cas system in Pseudomonas aeruginosa, elucidates how bacteria control the expression of nucleolytic host defence systems to minimize the potential risks of self-targeting. 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 the regulation of 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 sigma(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 upon 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.