TY - JOUR
T1 - Quorum sensing controls the pseudomonas aeruginosa CRISPR-Cas adaptive immune system
AU - Høyland-Kroghsbo, Nina M.
AU - Paczkowski, Jon
AU - Mukherjee, Sampriti
AU - Broniewski, Jenny
AU - Westra, Edze
AU - Bondy-Denomy, Joseph
AU - Bassler, Bonnie L.
N1 - Funding Information:
We thank Dr. Julie S. Valastyan, Dr. Chari D. Smith, and other members of the B.L.B. group for helpful suggestions; Dr. Sine Lo Svenningsen for encouraging initial development of the hypothesis; and Dr. George O'Toole and Dr. Joseph Mougous for providing strains. This work was supported by the Howard Hughes Medical Institute, NIH Grant 2R37GM065859, and National Science Foundation Grant MCB-0948112 (to B.L.B.); a Danish Council for Independent Research, Postdoctoral Research Fellowship DFF-4090-00265, administered by the University of Copenhagen (to N.M.H.-K.); and a Jane Coffin Child Memorial Fund for Biomedical Research Postdoctoral fellowship (to J.P.). E.W. was supported by the Natural Environment Research Council, the Wellcome Trust, and the Biotechnology and Biological Sciences Research Council. J.B.-D. was supported by the University of California, San Francisco Program for Breakthrough Biomedical Research, funded in part by the Sandler Foundation, and an NIH Office of the Director Early Independence Award (DP5-OD021344).
PY - 2017/1/3
Y1 - 2017/1/3
N2 - 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 proand 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.
AB - 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 proand 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.
KW - Immunity|
KW - Phage|phage defense
KW - Quorum sensing|crispr|
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U2 - 10.1073/pnas.1617415113
DO - 10.1073/pnas.1617415113
M3 - Article
C2 - 27849583
AN - SCOPUS:85007529875
SN - 0027-8424
VL - 114
SP - 131
EP - 135
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 1
ER -