6lhy › Citations

Structural and functional evidence of bacterial antiphage protection by Thoeris defense system via NAD+ degradation.

<div class='caption-title'>ThsA cleaves NAD+ into Nam and ADPR.</div>
<div class='caption-title'>Crystal structure of ThsA.</div>
<div class='caption-title'>NAD+ cleavage activity is intrinsic to the N-terminal sirtuin-like domain of ThsA.</div>
Ka D, Oh H, Park E, Kim JH, Bae E
OpenAccess logo Nat Commun 11 2816 (2020)
Cited: 48 times
EuropePMC logo PMID: 32499527

Abstract

The intense arms race between bacteria and phages has led to the development of diverse antiphage defense systems in bacteria. Unlike well-known restriction-modification and CRISPR-Cas systems, recently discovered systems are poorly characterized. One such system is the Thoeris defense system, which consists of two genes, thsA and thsB. Here, we report structural and functional analyses of ThsA and ThsB. ThsA exhibits robust NAD+ cleavage activity and a two-domain architecture containing sirtuin-like and SLOG-like domains. Mutation analysis suggests that NAD+ cleavage is linked to the antiphage function of Thoeris. ThsB exhibits a structural resemblance to TIR domain proteins such as nucleotide hydrolases and Toll-like receptors, but no enzymatic activity is detected in our in vitro assays. These results further our understanding of the molecular mechanism underlying the Thoeris defense system, highlighting a unique strategy for bacterial antiphage resistance via NAD+ degradation.

Articles - 6lhy mentioned but not cited (4)

  1. Cryo-EM structure of an active bacterial TIR-STING filament complex. Morehouse BR, Yip MCJ, Keszei AFA, McNamara-Bordewick NK, Shao S, Kranzusch PJ. Nature 608 803-807 (2022)
  2. Plant and prokaryotic TIR domains generate distinct cyclic ADPR NADase products. Bayless AM, Chen S, Ogden SC, Xu X, Sidda JD, Manik MK, Li S, Kobe B, Ve T, Song L, Grant M, Wan L, Nishimura MT. Sci Adv 9 eade8487 (2023)
  3. Structural characterization of macro domain-containing Thoeris antiphage defense systems. Shi Y, Masic V, Mosaiab T, Rajaratman P, Hartley-Tassell L, Sorbello M, Goulart CC, Vasquez E, Mishra BP, Holt S, Gu W, Kobe B, Ve T. Sci Adv 10 eadn3310 (2024)
  4. A bacterial TIR-based immune system senses viral capsids to initiate defense. Roberts CG, Fishman CB, Banh DV, Marraffini LA. bioRxiv 2024.07.29.605636 (2024)


Reviews citing this publication (10)

  1. Mechanisms and clinical importance of bacteriophage resistance. Egido JE, Costa AR, Aparicio-Maldonado C, Haas PJ, Brouns SJJ. FEMS Microbiol Rev 46 fuab048 (2022)
  2. Bacterial defences: mechanisms, evolution and antimicrobial resistance. Smith WPJ, Wucher BR, Nadell CD, Foster KR. Nat Rev Microbiol 21 519-534 (2023)
  3. Structural Evolution of TIR-Domain Signalosomes. Nimma S, Gu W, Maruta N, Li Y, Pan M, Saikot FK, Lim BYJ, McGuinness HY, Zaoti ZF, Li S, Desa S, Manik MK, Nanson JD, Kobe B. Front Immunol 12 784484 (2021)
  4. Bacterial origins of cyclic nucleotide-activated antiviral immune signaling. Patel DJ, Yu Y, Jia N. Mol Cell 82 4591-4610 (2022)
  5. Recent advances and perspectives in nucleotide second messenger signaling in bacteria. Hengge R, Pruteanu M, Stülke J, Tschowri N, Turgay K. Microlife 4 uqad015 (2023)
  6. Conservation and similarity of bacterial and eukaryotic innate immunity. Ledvina HE, Whiteley AT. Nat Rev Microbiol 22 420-434 (2024)
  7. Plant NLR immunity activation and execution: a biochemical perspective. Locci F, Parker JE. Open Biol 14 230387 (2024)
  8. The arms race between bacteria CBASS and bacteriophages. Wang L, Zhang L. Front Immunol 14 1224341 (2023)
  9. Structural characterization of TIR-domain signalosomes through a combination of structural biology approaches. Bhatt A, Mishra BP, Gu W, Sorbello M, Xu H, Ve T, Kobe B. IUCrJ 11 695-707 (2024)
  10. TIR enzymatic functions: signaling molecules and receptor mechanisms. Wan L. aBIOTECH 4 172-175 (2023)

Articles citing this publication (34)

  1. Antiviral activity of bacterial TIR domains via immune signalling molecules. Ofir G, Herbst E, Baroz M, Cohen D, Millman A, Doron S, Tal N, Malheiro DBA, Malitsky S, Amitai G, Sorek R. Nature 600 116-120 (2021)
  2. Identification and classification of antiviral defence systems in bacteria and archaea with PADLOC reveals new system types. Payne LJ, Todeschini TC, Wu Y, Perry BJ, Ronson CW, Fineran PC, Nobrega FL, Jackson SA. Nucleic Acids Res 49 10868-10878 (2021)
  3. Short prokaryotic Argonaute systems trigger cell death upon detection of invading DNA. Koopal B, Potocnik A, Mutte SK, Aparicio-Maldonado C, Lindhoud S, Vervoort JJM, Brouns SJJ, Swarts DC. Cell 185 1471-1486.e19 (2022)
  4. Viruses inhibit TIR gcADPR signalling to overcome bacterial defence. Leavitt A, Yirmiya E, Amitai G, Lu A, Garb J, Herbst E, Morehouse BR, Hobbs SJ, Antine SP, Sun ZJ, Kranzusch PJ, Sorek R. Nature 611 326-331 (2022)
  5. Cyclic nucleotide-induced helical structure activates a TIR immune effector. Hogrel G, Guild A, Graham S, Rickman H, Grüschow S, Bertrand Q, Spagnolo L, White MF. Nature 608 808-812 (2022)
  6. Short prokaryotic Argonautes provide defence against incoming mobile genetic elements through NAD+ depletion. Zaremba M, Dakineviciene D, Golovinas E, Zagorskaitė E, Stankunas E, Lopatina A, Sorek R, Manakova E, Ruksenaite A, Silanskas A, Asmontas S, Grybauskas A, Tylenyte U, Jurgelaitis E, Grigaitis R, Timinskas K, Venclovas Č, Siksnys V. Nat Microbiol 7 1857-1869 (2022)
  7. A nucleotide-sensing endonuclease from the Gabija bacterial defense system. Cheng R, Huang F, Wu H, Lu X, Yan Y, Yu B, Wang X, Zhu B. Nucleic Acids Res 49 5216-5229 (2021)
  8. Structural insights into mechanisms of Argonaute protein-associated NADase activation in bacterial immunity. Wang X, Li X, Yu G, Zhang L, Zhang C, Wang Y, Liao F, Wen Y, Yin H, Liu X, Wei Y, Li Z, Deng Z, Zhang H. Cell Res 33 699-711 (2023)
  9. Prokaryotic Argonaute Proteins as a Tool for Biotechnology. Kropocheva EV, Lisitskaya LA, Agapov AA, Musabirov AA, Kulbachinskiy AV, Esyunina DM. Mol Biol 56 854-873 (2022)
  10. Catalytically inactive long prokaryotic Argonaute systems employ distinct effectors to confer immunity via abortive infection. Song X, Lei S, Liu S, Liu Y, Fu P, Zeng Z, Yang K, Chen Y, Li M, She Q, Han W. Nat Commun 14 6970 (2023)
  11. Apprehending the NAD+-ADPr-Dependent Systems in the Virus World. Iyer LM, Burroughs AM, Anantharaman V, Aravind L. Viruses 14 1977 (2022)
  12. Activation of Thoeris antiviral system via SIR2 effector filament assembly. Tamulaitiene G, Sabonis D, Sasnauskas G, Ruksenaite A, Silanskas A, Avraham C, Ofir G, Sorek R, Zaremba M, Siksnys V. Nature 627 431-436 (2024)
  13. Products of gut microbial Toll/interleukin-1 receptor domain NADase activities in gnotobiotic mice and Bangladeshi children with malnutrition. Weagley JS, Zaydman M, Venkatesh S, Sasaki Y, Damaraju N, Yenkin A, Buchser W, Rodionov DA, Osterman A, Ahmed T, Barratt MJ, DiAntonio A, Milbrandt J, Gordon JI. Cell Rep 39 110738 (2022)
  14. Functionally comparable but evolutionarily distinct nucleotide-targeting effectors help identify conserved paradigms across diverse immune systems. Nicastro GG, Burroughs AM, Iyer LM, Aravind L. Nucleic Acids Res 51 11479-11503 (2023)
  15. Insights into the modulation of bacterial NADase activity by phage proteins. Yin H, Li X, Wang X, Zhang C, Gao J, Yu G, He Q, Yang J, Liu X, Wei Y, Li Z, Zhang H. Nat Commun 15 2692 (2024)
  16. Structural and functional investigation of GajB protein in Gabija anti-phage defense. Oh H, Koo J, An SY, Hong SH, Suh JY, Bae E. Nucleic Acids Res 51 11941-11951 (2023)
  17. The missing part: the Archaeoglobus fulgidus Argonaute forms a functional heterodimer with an N-L1-L2 domain protein. Manakova E, Golovinas E, Pocevičiūtė R, Sasnauskas G, Silanskas A, Rutkauskas D, Jankunec M, Zagorskaitė E, Jurgelaitis E, Grybauskas A, Venclovas Č, Zaremba M. Nucleic Acids Res 52 2530-2545 (2024)
  18. Defense and anti-defense mechanisms of bacteria and bacteriophages. Wang X, Leptihn S. J Zhejiang Univ Sci B 25 181-196 (2024)
  19. Microcalorimetry: A Novel Application to Measure In Vitro Phage Susceptibility of Staphylococcus aureus in Human Serum. Molendijk MM, Phan MVT, Bode LGM, Strepis N, Prasad DK, Worp N, Nieuwenhuijse DF, Schapendonk CME, Boekema BKHL, Verbon A, Koopmans MPG, Graaf M, van Wamel WJB. Viruses 15 14 (2022)
  20. Structural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system. Zhang JT, Liu XY, Li Z, Wei XY, Song XY, Cui N, Zhong J, Li H, Jia N. Nat Commun 15 2797 (2024)
  21. Structural basis of antiphage immunity generated by a prokaryotic Argonaute-associated SPARSA system. Zhen X, Xu X, Ye L, Xie S, Huang Z, Yang S, Wang Y, Li J, Long F, Ouyang S. Nat Commun 15 450 (2024)
  22. Molecular basis of bacterial DSR2 anti-phage defense and viral immune evasion. Huang J, Zhu K, Gao Y, Ye F, Li Z, Ge Y, Liu S, Yang J, Gao A. Nat Commun 15 3954 (2024)
  23. Characterization and genomic analysis of a novel lytic phage vB_PstM_ZRG1 infecting Stutzerimonas stutzeri, representing a new viral genus, Elithevirus. Chen Y, Guo R, Liang Y, Luo L, Han Y, Wang H, Zhang H, Liu Y, Zheng K, Shao H, Sung YY, Mok WJ, Wong LL, McMinn A, Wang M. Virus Res 334 199183 (2023)
  24. Characterization of the Structural Requirements for the NADase Activity of Bacterial Toll/IL-1R domains in a Course-based Undergraduate Research Experience. Vallejo-Schmidt T, Palm C, Obiorah T, Koudjra AR, Schmidt K, Scudder AH, Guzman-Cruz E, Ingram LP, Erickson BC, Akingbehin V, Riddick T, Hamilton S, Riaz T, Alexander Z, Anderson JT, Bader C, Calkins PH, Chaudhry SS, Collins H, Conteh M, Dada TA, David J, Fallah D, De Leon R, Duff R, Eromosele IR, Jones JK, Keshmiri N, Mercanti MA, Onwezi-Nwugwo J, Ojo MA, Pascoe ER, Poteat AM, Price SE, Riedlbauer D, Rolle LTA, Shoemaker P, Stefano A, Sterling MK, Sultana S, Toneygay L, Williams AN, Nallar S, Weldon JE, Snyder GA, Snyder MLD. Immunohorizons 8 563-576 (2024)
  25. Correlation of <i>Pseudomonas aeruginosa</i> Phage Resistance with the Numbers and Types of Antiphage Systems. Burke KA, Urick CD, Mzhavia N, Nikolich MP, Filippov AA. Int J Mol Sci 25 1424 (2024)
  26. Genomic analysis of Oceanotoga teriensis strain UFV_LIMV02, a multidrug-resistant thermophilic bacterium isolated from an offshore oil reservoir. Santos AJDC, Dias RS, da Silva CHM, Vidigal PMP, de Sousa MP, da Silva CC, de Paula SO. Access Microbiol 6 000801.v3 (2024)
  27. Genomic and taxonomic evaluation of 38 Treponema prophage sequences. Ridgway R, Lu H, Blower TR, Evans NJ, Ainsworth S. BMC Genomics 25 549 (2024)
  28. Increased mutations in lipopolysaccharide biosynthetic genes cause time-dependent development of phage resistance in Salmonella. Yu J, Zhang H, Ju Z, Huang J, Lin C, Wu J, Wu Y, Sun S, Wang H, Hao G, Zhang A. Antimicrob Agents Chemother 68 e0059423 (2024)
  29. Structural basis for the concerted antiphage activity in the SIR2-HerA system. Liao F, Yu G, Zhang C, Liu Z, Li X, He Q, Yin H, Liu X, Li Z, Zhang H. Nucleic Acids Res 52 11336-11348 (2024)
  30. Structural insights into activation mechanisms on NADase of the bacterial DSR2 anti-phage defense system. Zhang H, Li Y, Li L, Chen L, Zhu C, Sun L, Dong P, Jing D, Yang J, Fu L, Xiao F, Xia N, Li S, Zheng Q, Wu Y. Sci Adv 10 eadn5691 (2024)
  31. Tetramerization-dependent activation of the Sir2-associated short prokaryotic Argonaute immune system. Cui N, Zhang JT, Li Z, Wei XY, Wang J, Jia N. Nat Commun 15 8610 (2024)
  32. The Linguistics of Bacterial Conflict Systems Reveal Ancient Origins of Eukaryotic Innate Immunity. Kibby EM, Whiteley AT. J Bacteriol 202 e00507-20 (2020)
  33. The role of TIR domain-containing proteins in bacterial defense against phages. Wang S, Kuang S, Song H, Sun E, Li M, Liu Y, Xia Z, Zhang X, Wang X, Han J, Rao VB, Zou T, Tan C, Tao P. Nat Commun 15 7384 (2024)
  34. The structural basis of the activation and inhibition of DSR2 NADase by phage proteins. Wang R, Xu Q, Wu Z, Li J, Guo H, Liao T, Shi Y, Yuan L, Gao H, Yang R, Shi Z, Li F. Nat Commun 15 6185 (2024)


Quick links