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

TitleQuorum sensing controls the Pseudomonas aeruginosa CRISPR-Cas adaptive immune system.
Publication TypeJournal Article
Year of Publication2017
AuthorsHøyland-Kroghsbo, NM, Paczkowski, J, Mukherjee, S, Broniewski, J, Westra, E, Bondy-Denomy, J, Bassler, BL
JournalProc Natl Acad Sci U S A
Date Published2017 01 03
KeywordsClustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Cas Systems, Phage Therapy, Pseudomonas aeruginosa, Pseudomonas Infections, Quorum Sensing

<p>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.</p>

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID27849583
PubMed Central IDPMC5224376
Grant List / / Wellcome Trust / United Kingdom
DP5 OD021344 / OD / NIH HHS / United States
R01 GM065859 / GM / NIGMS NIH HHS / United States
R37 GM065859 / GM / NIGMS NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States