Controlling and Enhancing CRISPR Systems

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2020 Dec 17

PMID 33328654

Citations 51

Authors

Haridha Shivram

Brady F Cress

Gavin J Knott

Jennifer A Doudna

Affiliations

Soon will be listed here.

Abstract

Many bacterial and archaeal organisms use clustered regularly interspaced short palindromic repeats-CRISPR associated (CRISPR-Cas) systems to defend themselves from mobile genetic elements. These CRISPR-Cas systems are classified into six types based on their composition and mechanism. CRISPR-Cas enzymes are widely used for genome editing and offer immense therapeutic opportunity to treat genetic diseases. To realize their full potential, it is important to control the timing, duration, efficiency and specificity of CRISPR-Cas enzyme activities. In this Review we discuss the mechanisms of natural CRISPR-Cas regulatory biomolecules and engineering strategies that enhance or inhibit CRISPR-Cas immunity by altering enzyme function. We also discuss the potential applications of these CRISPR regulators and highlight unanswered questions about their evolution and purpose in nature.

Citing Articles

Assessing spacer acquisition rates in type I-E CRISPR arrays.

Peach L, Zhang H, Weaver B, Boedicker J Front Microbiol. 2025; 15:1498959.

PMID: 39902289 PMC: 11788318. DOI: 10.3389/fmicb.2024.1498959.

Genetic manipulation and tools in myxobacteria for the exploitation of secondary metabolism.

Yue X, Sheng D, Zhuo L, Li Y Eng Microbiol. 2024; 3(2):100075.

PMID: 39629250 PMC: 11610982. DOI: 10.1016/j.engmic.2023.100075.

Structural basis for regulation of a CBASS-CRISPR-Cas defense island by a transmembrane anti-σ factor and its ECF σ partner.

Bernal-Bernal D, Pantoja-Uceda D, Lopez-Alonso J, Lopez-Rojo A, Lopez-Ruiz J, Galbis-Martinez M Sci Adv. 2024; 10(43):eadp1053.

PMID: 39454004 PMC: 11506125. DOI: 10.1126/sciadv.adp1053.

Engineering probiotic Nissle 1917 to block transfer of multiple antibiotic resistance genes by exploiting a type I CRISPR-Cas system.

Fang M, Zhang R, Wang C, Liu Z, Fei M, Tang B Appl Environ Microbiol. 2024; 90(10):e0081124.

PMID: 39254327 PMC: 11497782. DOI: 10.1128/aem.00811-24.

Sub-MIC antibiotics increased the fitness cost of CRISPR-Cas in .

Yu T, Huang J, Huang X, Hao J, Zhang P, Guo T Front Microbiol. 2024; 15:1381749.

PMID: 39011146 PMC: 11246858. DOI: 10.3389/fmicb.2024.1381749.

References

Jansen R, van Embden J, Gaastra W, Schouls L . Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol. 2002; 43(6):1565-75. DOI: 10.1046/j.1365-2958.2002.02839.x. View

Mojica F, Diez-Villasenor C, Garcia-Martinez J, Soria E . Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J Mol Evol. 2005; 60(2):174-82. DOI: 10.1007/s00239-004-0046-3. View

Makarova K, Wolf Y, Iranzo J, Shmakov S, Alkhnbashi O, Brouns S . Evolutionary classification of CRISPR-Cas systems: a burst of class 2 and derived variants. Nat Rev Microbiol. 2019; 18(2):67-83. PMC: 8905525. DOI: 10.1038/s41579-019-0299-x. View

Vale P, Lafforgue G, Gatchitch F, Gardan R, Moineau S, Gandon S . Costs of CRISPR-Cas-mediated resistance in Streptococcus thermophilus. Proc Biol Sci. 2015; 282(1812):20151270. PMC: 4528535. DOI: 10.1098/rspb.2015.1270. View

Westra E, Pul U, Heidrich N, Jore M, Lundgren M, Stratmann T . H-NS-mediated repression of CRISPR-based immunity in Escherichia coli K12 can be relieved by the transcription activator LeuO. Mol Microbiol. 2010; 77(6):1380-93. DOI: 10.1111/j.1365-2958.2010.07315.x. View

Medina-Aparicio L, Rebollar-Flores J, Gallego-Hernandez A, Vazquez A, Olvera L, Gutierrez-Rios R . The CRISPR/Cas immune system is an operon regulated by LeuO, H-NS, and leucine-responsive regulatory protein in Salmonella enterica serovar Typhi. J Bacteriol. 2011; 193(10):2396-407. PMC: 3133143. DOI: 10.1128/JB.01480-10. View

Liu T, Liu Z, Ye Q, Pan S, Wang X, Li Y . Coupling transcriptional activation of CRISPR-Cas system and DNA repair genes by Csa3a in Sulfolobus islandicus. Nucleic Acids Res. 2017; 45(15):8978-8992. PMC: 5587795. DOI: 10.1093/nar/gkx612. View

He F, Vestergaard G, Peng W, She Q, Peng X . CRISPR-Cas type I-A Cascade complex couples viral infection surveillance to host transcriptional regulation in the dependence of Csa3b. Nucleic Acids Res. 2016; 45(4):1902-1913. PMC: 5389559. DOI: 10.1093/nar/gkw1265. View

Patterson A, Chang J, Taylor C, Fineran P . Regulation of the Type I-F CRISPR-Cas system by CRP-cAMP and GalM controls spacer acquisition and interference. Nucleic Acids Res. 2015; 43(12):6038-48. PMC: 4499141. DOI: 10.1093/nar/gkv517. View

10.

Perez-Rodriguez R, Haitjema C, Huang Q, Nam K, Bernardis S, Ke A . Envelope stress is a trigger of CRISPR RNA-mediated DNA silencing in Escherichia coli. Mol Microbiol. 2011; 79(3):584-99. PMC: 3040579. DOI: 10.1111/j.1365-2958.2010.07482.x. View

11.

Patterson A, Jackson S, Taylor C, Evans G, Salmond G, Przybilski R . Quorum Sensing Controls Adaptive Immunity through the Regulation of Multiple CRISPR-Cas Systems. Mol Cell. 2016; 64(6):1102-1108. PMC: 5179492. DOI: 10.1016/j.molcel.2016.11.012. View

12.

Hoyland-Kroghsbo N, Paczkowski J, Mukherjee S, Broniewski J, Westra E, Bondy-Denomy J . Quorum sensing controls the Pseudomonas aeruginosa CRISPR-Cas adaptive immune system. Proc Natl Acad Sci U S A. 2016; 114(1):131-135. PMC: 5224376. DOI: 10.1073/pnas.1617415113. View

13.

Borges A, Castro B, Govindarajan S, Solvik T, Escalante V, Bondy-Denomy J . Bacterial alginate regulators and phage homologs repress CRISPR-Cas immunity. Nat Microbiol. 2020; 5(5):679-687. PMC: 7190418. DOI: 10.1038/s41564-020-0691-3. View

14.

Hoyland-Kroghsbo N, Munoz K, Bassler B . Temperature, by Controlling Growth Rate, Regulates CRISPR-Cas Activity in Pseudomonas aeruginosa. mBio. 2018; 9(6). PMC: 6234860. DOI: 10.1128/mBio.02184-18. View

15.

Koonin E, Makarova K . Discovery of Oligonucleotide Signaling Mediated by CRISPR-Associated Polymerases Solves Two Puzzles but Leaves an Enigma. ACS Chem Biol. 2017; 13(2):309-312. PMC: 11075118. DOI: 10.1021/acschembio.7b00713. View

16.

Lin P, Pu Q, Wu Q, Zhou C, Wang B, Schettler J . High-throughput screen reveals sRNAs regulating crRNA biogenesis by targeting CRISPR leader to repress Rho termination. Nat Commun. 2019; 10(1):3728. PMC: 6700203. DOI: 10.1038/s41467-019-11695-8. View

17.

Bondy-Denomy J, Davidson A, Doudna J, Fineran P, Maxwell K, Moineau S . A Unified Resource for Tracking Anti-CRISPR Names. CRISPR J. 2019; 1:304-305. PMC: 10625466. DOI: 10.1089/crispr.2018.0043. View

18.

Chowdhury S, Carter J, Rollins M, Golden S, Jackson R, Hoffmann C . Structure Reveals Mechanisms of Viral Suppressors that Intercept a CRISPR RNA-Guided Surveillance Complex. Cell. 2017; 169(1):47-57.e11. PMC: 5478280. DOI: 10.1016/j.cell.2017.03.012. View

19.

Rollins M, Chowdhury S, Carter J, Golden S, Miettinen H, Santiago-Frangos A . Structure Reveals a Mechanism of CRISPR-RNA-Guided Nuclease Recruitment and Anti-CRISPR Viral Mimicry. Mol Cell. 2019; 74(1):132-142.e5. PMC: 6521718. DOI: 10.1016/j.molcel.2019.02.001. View

20.

Wang X, Yao D, Xu J, Li A, Xu J, Fu P . Structural basis of Cas3 inhibition by the bacteriophage protein AcrF3. Nat Struct Mol Biol. 2016; 23(9):868-70. DOI: 10.1038/nsmb.3269. View