» Articles » PMID: 31474367

Anti-CRISPR-Associated Proteins Are Crucial Repressors of Anti-CRISPR Transcription

Overview
Journal Cell
Publisher Cell Press
Specialty Cell Biology
Date 2019 Sep 3
PMID 31474367
Citations 61
Authors
Affiliations
Soon will be listed here.
Abstract

Phages express anti-CRISPR (Acr) proteins to inhibit CRISPR-Cas systems that would otherwise destroy their genomes. Most acr genes are located adjacent to anti-CRISPR-associated (aca) genes, which encode proteins with a helix-turn-helix DNA-binding motif. The conservation of aca genes has served as a signpost for the identification of acr genes, but the function of the proteins encoded by these genes has not been investigated. Here we reveal that an acr-associated promoter drives high levels of acr transcription immediately after phage DNA injection and that Aca proteins subsequently repress this transcription. Without Aca activity, this strong transcription is lethal to a phage. Our results demonstrate how sufficient levels of Acr proteins accumulate early in the infection process to inhibit existing CRISPR-Cas complexes in the host cell. They also imply that the conserved role of Aca proteins is to mitigate the deleterious effects of strong constitutive transcription from acr promoters.

Citing Articles

Current Updates of CRISPR/Cas System and Anti-CRISPR Proteins: Innovative Applications to Improve the Genome Editing Strategies.

Allemailem K, Almatroudi A, Alrumaihi F, Alradhi A, Theyab A, Algahtani M Int J Nanomedicine. 2024; 19:10185-10212.

PMID: 39399829 PMC: 11471075. DOI: 10.2147/IJN.S479068.


Diverse anti-defence systems are encoded in the leading region of plasmids.

Samuel B, Mittelman K, Croitoru S, Ben Haim M, Burstein D Nature. 2024; 635(8037):186-192.

PMID: 39385022 PMC: 11541004. DOI: 10.1038/s41586-024-07994-w.


Phage anti-CRISPR control by an RNA- and DNA-binding helix-turn-helix protein.

Birkholz N, Kamata K, Feussner M, Wilkinson M, Cuba Samaniego C, Migur A Nature. 2024; 631(8021):670-677.

PMID: 38987591 DOI: 10.1038/s41586-024-07644-1.


A new anti-CRISPR gene promotes the spread of drug-resistance plasmids in Klebsiella pneumoniae.

Jiang C, Yu C, Sun S, Lin J, Cai M, Wei Z Nucleic Acids Res. 2024; 52(14):8370-8384.

PMID: 38888121 PMC: 11317147. DOI: 10.1093/nar/gkae516.


Regulatory sequence-based discovery of anti-defense genes in archaeal viruses.

Bhoobalan-Chitty Y, Xu S, Martinez-Alvarez L, Karamycheva S, Makarova K, Koonin E Nat Commun. 2024; 15(1):3699.

PMID: 38698035 PMC: 11065993. DOI: 10.1038/s41467-024-48074-x.


References
1.
Sambrook J, Russell D . Purification of Bacteriophage λ Particles by Isopycnic Centrifugation through CsCl Gradients. CSH Protoc. 2012; 2006(1). DOI: 10.1101/pdb.prot3968. View

2.
Park C, Zhang J . High expression hampers horizontal gene transfer. Genome Biol Evol. 2012; 4(4):523-32. PMC: 3342876. DOI: 10.1093/gbe/evs030. View

3.
Lavigne R, Ceyssens P, Robben J . Phage proteomics: applications of mass spectrometry. Methods Mol Biol. 2008; 502:239-51. DOI: 10.1007/978-1-60327-565-1_14. View

4.
Greene A . CRISPR-Based Antibacterials: Transforming Bacterial Defense into Offense. Trends Biotechnol. 2017; 36(2):127-130. DOI: 10.1016/j.tibtech.2017.10.021. View

5.
Juranek S, Eban T, Altuvia Y, Brown M, Morozov P, Tuschl T . A genome-wide view of the expression and processing patterns of Thermus thermophilus HB8 CRISPR RNAs. RNA. 2012; 18(4):783-94. PMC: 3312565. DOI: 10.1261/rna.031468.111. View