Hampton, H. G., Watson, B. N. J. & Fineran, P. C. The arms race between bacteria and their phage foes. Nature 577, 327–336 (2020).
Georjon, H. & Bernheim, A. The highly diverse antiphage defence systems of bacteria. Nat. Rev. Microbiol. 21, 686–700 (2023).
Makarova, K. S., Wolf, Y. I. & Koonin, E. V. Comparative genomics of defence systems in archaea and bacteria. Nucleic Acids Res. 41, 4360–4377 (2013).
Makarova, K. S., Wolf, Y. I., Snir, S. & Koonin, E. V. Defence islands in bacterial and archaeal genomes and prediction of novel defence systems. J. Bacteriol. 193, 6039–6056 (2011).
Payne, L. J., Hughes, T. C., Fineran, P. C. & Jackson, S. A. New antiviral defences are genetically embedded within prokaryotic immune systems. Preprint at bioRxiv https://doi.org/10.1101/2024.01.29.577857 (2024).
Barrangou, R. et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science 315, 1709–1712 (2007).
Marraffini, L. A. & Sontheimer, E. J. CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science 322, 1843–1845 (2008).
Brouns, S. J. et al. Small CRISPR RNAs guide antiviral defence in prokaryotes. Science 321, 960–964 (2008).
Mojica, F. J. M., Diez-Villasenor, C., Garcia-Martinez, J. & Almendros, C. Short motif sequences determine the targets of the prokaryotic CRISPR defence system. Microbiology 155, 733–740 (2009).
Makarova, K. S. et al. An updated evolutionary classification of CRISPR–Cas systems including rare variants. Nat. Microbiol. 10, 3346–3361 (2025).
Altae-Tran, H. et al. Uncovering the functional diversity of rare CRISPR–Cas systems with deep terascale clustering. Science 382, eadi1910 (2023).
Shmakov, S. A. et al. Widespread CRISPR-derived RNA regulatory elements in CRISPR–Cas systems. Nucleic Acids Res. 51, 8150–8168 (2023).
Ratner, H. K. et al. Catalytically active Cas9 mediates transcriptional interference to facilitate bacterial virulence. Mol. Cell 75, 498–510.e5 (2019).
Li, M. et al. Toxin-antitoxin RNA pairs safeguard CRISPR–Cas systems. Science 372, eabe5601 (2021).
Liu, C. et al. Widespread RNA-based cas regulation monitors crRNA abundance and anti-CRISPR proteins. Cell Host Microbe 31, 1481–1493.e6 (2023).
Workman, R. E. et al. A natural single-guide RNA repurposes Cas9 to autoregulate CRISPR–Cas expression. Cell 184, 675–688.e19 (2021).
Wang, R. et al. Associate toxin-antitoxin with CRISPR–Cas to kill multidrug-resistant pathogens. Nat. Commun. 14, 2078 (2023).
Shu, X. et al. CRISPR-repressed toxin-antitoxin provides herd immunity against anti-CRISPR elements. Nat. Chem. Biol. 21, 337–347 (2025).
Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077–1084 (2020).
Tang, D. et al. Multiple enzymatic activities of a Sir2–HerA system cooperate for anti-phage defence. Mol. Cell 83, 4600–4613.e6 (2023).
Garb, J. et al. Multiple phage resistance systems inhibit infection via SIR2-dependent NAD+ depletion. Nat. Microbiol. 7, 1849–1856 (2022).
Rousset, F. et al. TIR signaling activates caspase-like immunity in bacteria. Science 387, 510–516 (2025).
Hochstrasser, M. L., Taylor, D. W., Kornfeld, J. E., Nogales, E. & Doudna, J. A. DNA targeting by a minimal CRISPR RNA-guided cascade. Mol. Cell 63, 840–851 (2016).
Csorgo, B. et al. A compact Cascade–Cas3 system for targeted genome engineering. Nat. Methods 17, 1183–1190 (2020).
Pagotto, F. J., Salimnia, H., Totten, P. A. & Dillon, J. R. Stable shuttle vectors for Neisseria gonorrhoeae, Haemophilus spp. and other bacteria based on a single origin of replication. Gene 244, 13–19 (2000).
Tesson, F. et al. Systematic and quantitative view of the antiviral arsenal of prokaryotes. Nat. Commun. 13, 2561 (2022).
Durmaz, E. & Klaenhammer, T. R. Abortive phage resistance mechanism AbiZ speeds the lysis clock to cause premature lysis of phage-infected Lactococcus lactis. J. Bacteriol. 189, 1417–1425 (2007).
Rousset, F. et al. A conserved family of immune effectors cleaves cellular ATP upon viral infection. Cell 186, 3619–3631.e13 (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, 1568–1579 (2022).
Hermoso, J. A. et al. Insights into pneumococcal pathogenesis from the crystal structure of the modular teichoic acid phosphorylcholine esterase Pce. Nat. Struct. Mol. Biol. 12, 533–538 (2005).
Yirmiya, E. et al. Systematic discovery of TIR-based immune signaling systems in bacteria. Preprint at bioRxiv https://doi.org/10.64898/2025.12.03.692087 (2025).
Roberts, C. G. et al. Bacterial TIR-based immune systems sense phage capsids to initiate defence. Nat. Microbiol. 10, 2892–2902 (2025).
Meyer, J. et al. Characterization of MDAPhi, a temperate filamentous bacteriophage of Neisseria meningitidis. Microbiology 162, 268–282 (2016).
Bille, E. et al. A virulence-associated filamentous bacteriophage of Neisseria meningitidis increases host-cell colonisation. PLoS Pathog. 13, e1006495 (2017).
Zhou, X. et al. Cas9 senses CRISPR RNA abundance to regulate CRISPR spacer acquisition. Nature 647, 1054–1062 (2025).
Leon, L. M., Park, A. E., Borges, A. L., Zhang, J. Y. & Bondy-Denomy, J. Mobile element warfare via CRISPR and anti-CRISPR in Pseudomonas aeruginosa. Nucleic Acids Res. 49, 2114–2125 (2021).
Gussow, A. B. et al. Machine-learning approach expands the repertoire of anti-CRISPR protein families. Nat. Commun. 11, 3784 (2020).
Hu, C. et al. Exploiting activation and inactivation mechanisms in type I-C CRISPR–Cas3 for genome-editing applications. Mol. Cell 84, 463–475.e5 (2024).
Sakaguchi, S., Yamaguchi, T., Nomura, T. & Ono, M. Regulatory T cells and immune tolerance. Cell 133, 775–787 (2008).
Doron, S. et al. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 359, eaar4120 (2018).
Westra, E. R. et al. H-NS-mediated repression of CRISPR-based immunity in Escherichia coli K12 can be relieved by the transcription activator LeuO. Mol. Microbiol. 77, 1380–1393 (2010).
Beck, I. N., Picton, D. M. & Blower, T. R. Crystal structure of the BREX phage defence protein BrxA. Curr. Res. Struct. Biol. 4, 211–219 (2022).
Aframian, N., Omer Bendori, S., Hen, T., Guler, P. & Eldar, A. Expression level of anti-phage defence systems controls a trade-off between protection range and autoimmunity. Nat. Microbiol. 10, 1954–1962 (2025).
Burman, N. et al. A virally encoded tRNA neutralizes the PARIS antiviral defence system. Nature 634, 424–431 (2024).
Deep, A., Liang, Q., Enustun, E., Pogliano, J. & Corbett, K. D. Architecture and activation mechanism of the bacterial PARIS defence system. Nature 634, 432–439 (2024).
Ledvina, H. E. & Whiteley, A. T. Conservation and similarity of bacterial and eukaryotic innate immunity. Nat. Rev. Microbiol. 22, 420–434 (2024).
Gaidt, M. M. et al. Self-guarding of MORC3 enables virulence factor-triggered immunity. Nature 600, 138–142 (2021).
Hu, C. et al. Craspase is a CRISPR RNA-guided, RNA-activated protease. Science 377, 1278–1285 (2022).
Niewoehner, O. et al. Type III CRISPR–Cas systems produce cyclic oligoadenylate second messengers. Nature 548, 543–548 (2017).
Lopatina, A., Tal, N. & Sorek, R. Abortive infection: bacterial suicide as an antiviral immune strategy. Annu. Rev. Virol. 7, 371–384 (2020).
Dillard, J. P. & Chan, J. M. Genetic manipulation of Neisseria gonorrhoeae and commensal Neisseria species. Curr. Protoc. 4, e70000 (2024).
Zhang, Y. et al. Processing-independent CRISPR RNAs limit natural transformation in Neisseria meningitidis. Mol. Cell 50, 488–503 (2013).
Li, Q. et al. A modified pCas/pTargetF system for CRISPR–Cas9-assisted genome editing in Escherichia coli. Acta Biochim. Biophy. Sin. 53, 620–627 (2021).
Tan, R. et al. Cas11 enables genome engineering in human cells with compact CRISPR–Cas3 systems. Mol. Cell 82, 852–867.e5 (2022).

