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Proc Natl Acad Sci U S A. 2017 Jan 3;114(1):131-135. doi: 10.1073/pnas.1617415113. Epub 2016 Nov 14.

Quorum sensing controls the Pseudomonas aeruginosa CRISPR-Cas adaptive immune system.

Author information

1
Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
2
Biosciences, Environment and Sustainability Institute, University of Exeter, Penryn TR10 9FE, United Kingdom.
3
Department of Microbiology and Immunology, University of California, San Francisco, CA 94158.
4
Department of Molecular Biology, Princeton University, Princeton, NJ 08544; bbassler@princeton.edu.
5
Howard Hughes Medical Institute, Chevy Chase, MD 20815.

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.

KEYWORDS:

CRISPR; immunity; phage; phage defense; quorum sensing

Comment in

PMID:
27849583
PMCID:
PMC5224376
DOI:
10.1073/pnas.1617415113
[Indexed for MEDLINE]
Free PMC Article

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