Georjon, H. & Bernheim, A. The highly diverse antiphage defence systems of bacteria. Nat. Rev. Microbiol. 21, 686â700 (2023).
Hampton, H. G., Watson, B. N. J. & Fineran, P. C. The arms race between bacteria and their phage foes. Nature 577, 327â336 (2020).
Gao, L. A. et al. Prokaryotic innate immunity through pattern recognition of conserved viral proteins. Science 377, eabm4096 (2022).
Doron, S. et al. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 359, eaar4120 (2018).
Rousset, F. et al. Phages and their satellites encode hotspots of antiviral systems. Cell Host Microbe 30, 740â753 (2022).
Gao, Z. & Feng, Y. Bacteriophage strategies for overcoming host antiviral immunity. Front. Microbiol. 14, 1211793 (2023).
Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat. Microbiol. 7, 1568â1579 (2022).
Makarova, K. S., Wolf, Y. I., Snir, S. & Koonin, E. V. Defense islands in bacterial and archaeal genomes and prediction of novel defense systems. J. Bacteriol. 193, 6039â6056 (2011).
Benler, S. et al. Cargo genes of Tn7-like transposons comprise an enormous diversity of defense systems, mobile genetic elements, and antibiotic resistance genes. mBio 12, e0293821 (2021).
Wu, Y. et al. Bacterial defense systems exhibit synergistic anti-phage activity. Cell Host Microbe 32, 557â572 (2024).
Lau, R. K. et al. Structure and mechanism of a cyclic trinucleotide-activated bacterial endonuclease mediating bacteriophage immunity. Mol. Cell 77, 723â733 (2020).
Lopatina, A., Tal, N. & Sorek, R. Abortive infection: bacterial suicide as an antiviral immune strategy. Annu. Rev. Virol. 7, 371â384 (2020).
Makarova, K. S., Anantharaman, V., Grishin, N. V., Koonin, E. V. & Aravind, L. CARF and WYL domains: ligand-binding regulators of prokaryotic defense systems. Front. Genet. 5, 102 (2014).
Bondy-Denomy, J. et al. Prophages mediate defense against phage infection through diverse mechanisms. ISME J. 10, 2854â2866 (2016).
Atanasiu, C., Su, T.-J., Sturrock, S. S. & Dryden, D. T. F. Interaction of the ocr gene 0.3 protein of bacteriophage T7 with EcoKI restriction/modification enzyme. Nucleic Acids Res. 30, 3936â3944 (2002).
Walkinshaw, M. D. et al. Structure of Ocr from bacteriophage T7, a protein that mimics B-form DNA. Mol. Cell 9, 187â194 (2002).
Isaev, A. et al. Phage T7 DNA mimic protein Ocr is a potent inhibitor of BREX defence. Nucleic Acids Res. 48, 7601â7602 (2020).
Song, S. & Wood, T. K. A primary physiological role of toxin/antitoxin systems is phage inhibition. Front. Microbiol. 11, 1895 (2020).
Hopfner, K.-P. & Tainer, J. A. Rad50/SMC proteins and ABC transporters: unifying concepts from high-resolution structures. Curr. Opin. Struct. Biol. 13, 249â255 (2003).
Deep, A. et al. The SMC-family Wadjet complex protects bacteria from plasmid transformation by recognition and cleavage of closed-circular DNA. Mol. Cell 82, 4145â4159.e7 (2022).
Hopfner, K. P. et al. Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily. Cell 101, 789â800 (2000).
Zawadzka, K. et al. MukB ATPases are regulated independently by the N- and C-terminal domains of MukF kleisin. eLife 7, e31522 (2018).
Schiltz, C. J., Adams, M. C. & Chappie, J. S. The full-length structure of Thermus scotoductus OLD defines the ATP hydrolysis properties and catalytic mechanism of class 1 OLD family nucleases. Nucleic Acids Res. 48, 2762â2776 (2020).
Oerum, S. et al. Structures of B. subtilis maturation RNases captured on 50S ribosome with pre-rRNAs. Mol. Cell 80, 227â236 (2020).
Ho, C.-H., Wang, H.-C., Ko, T.-P., Chang, Y.-C. & Wang, A. H.-J. The T4 phage DNA mimic protein Arn inhibits the DNA binding activity of the bacterial histone-like protein H-NS. J. Biol. Chem. 289, 27046â27054 (2014).
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583â589 (2021).
Nonejuie, P., Burkart, M., Pogliano, K. & Pogliano, J. Bacterial cytological profiling rapidly identifies the cellular pathways targeted by antibacterial molecules. Proc. Natl Acad. Sci. USA 110, 16169â16174 (2013).
Burman, N. et al. A virally-encoded tRNA neutralizes the PARIS antiviral defence system. Nature, https://doi.org/10.1038/s41586-024-07874-3 (2024).
Bregegere, F. Bacteriophage P2-lambda interference: inhibition of protein synthesis involves transfer RNA inactivation. J. Mol. Biol. 90, 459â467 (1974).
Ernits, K. et al. The structural basis of hyperpromiscuity in a core combinatorial network of type II toxin-antitoxin and related phage defense systems. Proc. Natl Acad. Sci. USA 120, e2305393120 (2023).
Sironi, G. Mutants of Escherichia coli unable to be lysogenized by the temperate bacteriophage P2. Virology 37, 163â176 (1969).
Krishnan, A., Burroughs, A. M., Iyer, L. M. & Aravind, L. Comprehensive classification of ABC ATPases and their functional radiation in nucleoprotein dynamics and biological conflict systems. Nucleic Acids Res. 48, 10045â10075 (2020).
Deng, Y. M., Liu, C. Q. & Dunn, N. W. Genetic organization and functional analysis of a novel phage abortive infection system, AbiL, from Lactococcus lactis. J. Biotechnol. 67, 135â149 (1999).
Miller, W. G. et al. Diversity within the Campylobacter jejuni type I restriction-modification loci. Microbiology 151, 337â351 (2005).
Ogura, T. & Hiraga, S. Mini-F plasmid genes that couple host cell division to plasmid proliferation. Proc. Natl Acad. Sci. USA 80, 4784â4788 (1983).
Harms, A., Brodersen, D. E., Mitarai, N. & Gerdes, K. Toxins, targets, and triggers: an overview of toxin-antitoxin biology. Mol. Cell 70, 768â784 (2018).
Bobonis, J. et al. Bacterial retrons encode phage-defending tripartite toxin-antitoxin systems. Nature 609, 144â150 (2022).
Zhang, T. et al. Direct activation of a bacterial innate immune system by a viral capsid protein. Nature 612, 132â140 (2022).
Fineran, P. C. et al. The phage abortive infection system, ToxIN, functions as a protein-RNA toxin-antitoxin pair. Proc. Natl Acad. Sci. USA 106, 894â899 (2009).
LeRoux, M. et al. The DarTG toxin-antitoxin system provides phage defence by ADP-ribosylating viral DNA. Nat. Microbiol. 7, 1028â1040 (2022).
Pecota, D. C. & Wood, T. K. Exclusion of T4 phage by the hok/sok killer locus from plasmid R1. J. Bacteriol. 178, 2044â2050 (1996).
Ledvina, H. E. et al. An E1-E2 fusion protein primes antiviral immune signalling in bacteria. Nature 616, 319â325 (2023).
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290â296 (2017).
Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70â82 (2021).
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486â501 (2010).
Afonine, P. V. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallogr. D 74, 531â544 (2018).
Deep, A. et al. Structural, functional and biological insights into the role of Mycobacterium tuberculosis VapBC11 toxinâantitoxin system: targeting a tRNase to tackle mycobacterial adaptation. Nucleic Acids Res. 46, 11639â11655 (2018).
Mirdita, M. et al. ColabFold: making protein folding accessible to all. Nat. Methods 19, 679â682 (2022).
Steinegger, M. & Söding, J. MMseqs2 enables sensitive protein sequence searching for the analysis of massive data sets. Nat. Biotechnol. 35, 1026â1028 (2017).
Eastman, P. et al. OpenMM 7: rapid development of high performance algorithms for molecular dynamics. PLoS Comput. Biol. 13, e1005659 (2017).
Waterhouse, A. M., Procter, J. B., Martin, D. M. A., Clamp, M. & Barton, G. J. Jalview Version 2âa multiple sequence alignment editor and analysis workbench. Bioinformatics 25, 1189â1191 (2009).
Holm, L. Dali server: structural unification of protein families. Nucleic Acids Res. 50, W210âW215 (2022).
Ashkenazy, H. et al. ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules. Nucleic Acids Res. 44, W344âW350 (2016).
Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676â682 (2012).
Schiltz, C. J., Lee, A., Partlow, E. A., Hosford, C. J. & Chappie, J. S. Structural characterization of Class 2 OLD family nucleases supports a two-metal catalysis mechanism for cleavage. Nucleic Acids Res. 47, 9448â9463 (2019).
