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

TY - JOUR

T1 - Quorum sensing controls the Pseudomonas aeruginosa CRISPR-Cas adaptive immune system

AU - Høyland-Kroghsbo, Nina Molin

AU - Paczkowski, Jon

AU - Mukherjee, Sampriti

AU - Broniewski, Jenny

AU - Westra, Edze

AU - Bondy-Denomy, Joseph

AU - Bassler, Bonnie L.

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.

U2 - 10.1073/pnas.1617415113

DO - 10.1073/pnas.1617415113

M3 - Journal article

C2 - 27849583

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 -