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

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.quorum sensing | CRISPR | immunity | phage | phage defense

A Broad-Spectrum Inhibitor of CRISPR-Cas9

“…The absence of this mechanism is possibly because this strategy would be unable to interfere with CRISPR nucleases that were assembled prior to infection. Nonetheless, many CRISPR systems are tightly regulated and are often activated in response to cell density and other factors (Høyland-Kroghsbo et al, 2016; Patterson et al, 2016, 2017). Inhibition of crRNA binding could be an effective Acr method to inhibit those systems where RNP assembly coincides with phage infection, and such inhibitors may yet be discovered.…”

A Novel RAYM_RS09735/RAYM_RS09740 Two-Component Signaling System Regulates Gene Expression and Virulence in Riemerella anatipestifer

“…Recent studies have reported that quorum sensing has a role in controlling the Pseudomonas aeruginosa CRISPR-Cas adaptive immune system (Høyland-Kroghsbo et al, 2016) and the TCS BfiSR affects the production of proteins involved in virulence, post-translational modification, and quorum sensing (Petrova and Sauer, 2010). We therefore reasoned that TCS might also affect the CRISPR-Cas immune system of R. anatipestifer .…”

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