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

Nina Molin Høyland-Kroghsbo; Jon Paczkowski; Sampriti Mukherjee; Jenny Broniewski; Edze Westra; Joseph Bondy-Denomy; Bonnie L. Bassler

doi:10.1073/pnas.1617415113

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

Nina Molin Høyland-Kroghsbo, Jon Paczkowski, Sampriti Mukherjee, Jenny Broniewski, Edze Westra, Joseph Bondy-Denomy, Bonnie L. Bassler

106 Citationer (Scopus)

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 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.

Originalsprog	Engelsk
Tidsskrift	National Academy of Sciences. Proceedings
Vol/bind	114
Udgave nummer	1
Sider (fra-til)	131-135
Antal sider	5
ISSN	0027-8424
DOI	https://doi.org/10.1073/pnas.1617415113
Status	Udgivet - 3 jan. 2017
Udgivet eksternt	Ja

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10.1073/pnas.1617415113

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Citationsformater

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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.

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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.

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

Abstract

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