Title | Quorum sensing controls the Pseudomonas aeruginosa CRISPR-Cas adaptive immune system. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Høyland-Kroghsbo, NM, Paczkowski, J, Mukherjee, S, Broniewski, J, Westra, E, Bondy-Denomy, J, Bassler, BL |
Journal | Proc Natl Acad Sci U S A |
Volume | 114 |
Issue | 1 |
Pagination | 131-135 |
Date Published | 2017 Jan 03 |
ISSN | 1091-6490 |
Keywords | Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Cas Systems, Phage Therapy, Pseudomonas aeruginosa, Pseudomonas Infections, Quorum Sensing |
Abstract | <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> |
DOI | 10.1073/pnas.1617415113 |
Alternate Journal | Proc Natl Acad Sci U S A |
PubMed ID | 27849583 |
PubMed Central ID | PMC5224376 |
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 |