Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 1, Pages 131-135Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1617415113
Keywords
quorum sensing; CRISPR; immunity; phage; phage defense
Categories
Funding
- Howard Hughes Medical Institute, NIH [2R37GM065859]
- National Science Foundation [MCB-0948112]
- Danish Council for Independent Research [DFF-4090-00265]
- Jane Coffin Child Memorial Fund for Biomedical Research Postdoctoral fellowship
- Natural Environment Research Council
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council
- University of California
- San Francisco Program for Breakthrough Biomedical Research
- Sandler Foundation
- NIH Office of the Director Early Independence Award [DP5-OD021344]
- BBSRC [1622146, BB/N017412/1] Funding Source: UKRI
- NERC [NE/M018350/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [1622146, BB/N017412/1] Funding Source: researchfish
- Natural Environment Research Council [NE/M018350/1] Funding Source: researchfish
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [0948112] Funding Source: National Science Foundation
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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.
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