title: Quorum sensing controls the Pseudomonas aeruginosa CRISPR-Cas adaptive immune system.
abstract: CRISPR-Cas are prokaryotic adaptive immune systems that provide protection against bacteriophage (phage) and other parasites. Little is known about how CRISPR-Cas systems are regulated, preventing prediction of phage dynamics in nature and manipulation of phage resistance in clinical settings. Here, we show that the bacterium Pseudomonas aeruginosa PA14 uses the cell-cell communication process, called quorum sensing, to activate cas gene expression, to increase CRISPR-Cas targeting of foreign DNA, and to promote CRISPR adaptation, all at high cell density. This regulatory mechanism ensures maximum CRISPR-Cas function when bacterial populations are at highest risk for phage infection. We demonstrate that CRISPR-Cas activity and acquisition of resistance can be modulated by administration of pro- and antiquorum-sensing compounds. We propose that quorum-sensing inhibitors could be used to suppress the CRISPR-Cas adaptive immune system to enhance medical applications, including phage therapies.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
authors.forename: Nina M
authors.initials: NM
authors.lastname: Høyland-Kroghsbo
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
authors.forename: Jon
authors.initials: J
authors.lastname: Paczkowski
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
authors.forename: Sampriti
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Biosciences, Environment and Sustainability Institute, University of Exeter, Penryn TR10 9FE, United Kingdom.
authors.forename: Jenny
authors.initials: J
authors.lastname: Broniewski
authors.affiliation: Biosciences, Environment and Sustainability Institute, University of Exeter, Penryn TR10 9FE, United Kingdom.
authors.forename: Edze
authors.initials: E
authors.lastname: Westra
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, CA 94158.
authors.forename: Joseph
authors.initials: J
authors.lastname: Bondy-Denomy
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544; bbassler@princeton.edu.|Howard Hughes Medical Institute, Chevy Chase, MD 20815.
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Bassler
mesh_terms: D064113:CRISPR-Cas Systems / Q000235:genetics*; D064112:Clustered Regularly Interspaced Short Palindromic Repeats / Q000235:genetics*; D000071059:Phage Therapy; D011552:Pseudomonas Infections / Q000628:therapy / Q000821:virology; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D053038:Quorum Sensing / Q000187:drug effects / Q000235:genetics*
keywords: CRISPR; immunity; phage; phage defense; quorum sensing