CRISPR-Cas immunity in prokaryotes

Marraffini, Luciano A.

doi:10.1038/nature15386

Cited by 682 publications

(510 citation statements)

References 120 publications

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“…As one of the prokaryotic DNA sensing systems, CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated protein) provides adaptive immune protection and helps archaea and bacteria defend themselves against phage infection [1][2][3]. Depending on the architecture of the effector-CRISPR RNA (crRNA) interference module, different CRISPR-Cas systems could be assigned into two classes [1]: class 1 systems (multi-subunit complex, such as Cascade) [4,5] and class 2 systems (single enzyme, such as Cas9) [6,7].…”

Section: Introductionmentioning

confidence: 99%

Type V CRISPR-Cas Cpf1 endonuclease employs a unique mechanism for crRNA-mediated target DNA recognition

et al. 2016

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CRISPR-Cas9 and CRISPR-Cpf1 systems have been successfully harnessed for genome editing. In the CRIS-PR-Cas9 system, the preordered A-form RNA seed sequence and preformed protein PAM-interacting cleft are essential for Cas9 to form a DNA recognition-competent structure. Whether the CRISPR-Cpf1 system employs a similar mechanism for target DNA recognition remains unclear. Here, we have determined the crystal structure of Acidaminococcus sp. Cpf1 (AsCpf1) in complex with crRNA and target DNA. Structural comparison between the AsCpf1-crRNA-DNA ternary complex and the recently reported Lachnospiraceae bacterium Cpf1 (LbCpf1)-crRNA binary complex identifies a unique mechanism employed by Cpf1 for target recognition. The seed sequence required for initial DNA interrogation is disordered in the Cpf1-cRNA binary complex, but becomes ordered upon ternary complex formation. Further, the PAM interacting cleft of Cpf1 undergoes an "open-to-closed" conformational change upon target DNA binding, which in turn induces structural changes within Cpf1 to accommodate the ordered A-form seed RNA segment. This unique mechanism of target recognition by Cpf1 is distinct from that reported previously for Cas9.

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Section: Introductionmentioning

confidence: 99%

Type V CRISPR-Cas Cpf1 endonuclease employs a unique mechanism for crRNA-mediated target DNA recognition

et al. 2016

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“…CRISPR loci are transcribed and processed into short crRNA (CRISPR RNA) molecules, which associate with Cas proteins to form a surveillance immune complex [20]. Upon re-infection, crRNA guides Cas proteins to bind and cleave complementary phage DNA, resulting in phage resistance ( [21], reviewed in [22,23]). …”

Section: Introductionmentioning

confidence: 99%

Immigration of susceptible hosts triggers the evolution of alternative parasite defence strategies

et al. 2016

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Migration of hosts and parasites can have a profound impact on host-parasite ecological and evolutionary interactions. Using the bacterium Pseudomonas aeruginosa UCBPP-PA14 and its phage DMS3vir, we here show that immigration of naive hosts into coevolving populations of hosts and parasites can influence the mechanistic basis underlying host defence evolution. Specifically, we found that at high levels of bacterial immigration, bacteria switched from clustered regularly interspaced short palindromic repeats (CRISPR-Cas) to surface modification-mediated defence. This effect emerges from an increase in the force of infection, which tips the balance from CRISPR to surface modification-based defence owing to the induced and fixed fitness costs associated with these mechanisms, respectively.

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“…Upon reinfection, processed CRISPR RNAs (crRNAs) guide Cas proteins to cleave complementary parasite genomes, which provides the bacterium with immunity (3,4). Thus, CRISPR-Cas, by patrolling the cell, combats viral attacks and also enables the cell to avoid acquisition of foreign plasmids to which its ancestors have been exposed (5,6).…”

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confidence: 99%

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

Høyland‐Kroghsbo

Paczkowski

Mukherjee

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

251

223

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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

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CRISPR-Cas immunity in prokaryotes

Cited by 682 publications

References 120 publications

Type V CRISPR-Cas Cpf1 endonuclease employs a unique mechanism for crRNA-mediated target DNA recognition

Type V CRISPR-Cas Cpf1 endonuclease employs a unique mechanism for crRNA-mediated target DNA recognition

Immigration of susceptible hosts triggers the evolution of alternative parasite defence strategies

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

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