1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Microbiology
  4. Volume 78, 2024
  5. Article

Annual Review of Microbiology

Volume 78, 2024

DNA Phosphorothioate Modification Systems and Associated Phage Defense Systems

Abstract

In contrast to the well-known DNA methylation of nucleobases, DNA phosphorothioate (PT) modification occurs in the DNA sugar-phosphate backbone. The non-bridging oxygen is replaced by a sulfur atom, which increases the nuclease tolerance of the DNA. In recent years, we have witnessed advances in understanding of PT modification enzymes, the features of PT modification across prokaryotic genomes, and PT-related physiological functions. Although only a small fraction of modifiable recognition sites across bacterial genomes undergo PT modification, enzymes such as DndFGH and SspE can use this modification as a recognition marker to differentiate between self- and non-self-DNA, thus destroying PT-lacking invasive DNA and preventing autoimmunity. We highlight the molecular mechanisms of PT modification–associated defense systems. We also describe notable applications of PT systems in the engineering of phage-resistant bacterial strains, RNA editing, and nucleic acid detection.

Keyword(s): DNA phosphorothioate modification, DNA PT modification, DndFGH, phage-resistant strains, ScoMcrA, SspE, sulfur-binding domain
Loading

Article metrics loading...

/content/journals/10.1146/annurev-micro-041222-014330
2024-11-20
2024-12-09
Loading full text...

Full text loading...

/deliver/fulltext/micro/78/1/annurev-micro-041222-014330.html?itemId=/content/journals/10.1146/annurev-micro-041222-014330&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Antine SP, Johnson AG, Mooney SE, Leavitt A, Mayer ML, et al. 2024.. Structural basis of Gabija anti-phage defense and viral immune evasion. . Nature 625::360–65
     [Crossref] [Google Scholar]
  2. 2.
    Anton BP, Roberts RJ. 2021.. Beyond restriction modification: epigenomic roles of DNA methylation in prokaryotes. . Annu. Rev. Microbiol. 75::129–49
     [Crossref] [Google Scholar]
  3. 3.
    Bair CL, Black LW. 2007.. A type IV modification dependent restriction nuclease that targets glucosylated hydroxymethyl cytosine modified DNAs. . JMB 366::768–78
     [Crossref] [Google Scholar]
  4. 4.
    Baltz RH. 2018.. Bacteriophage-resistant industrial fermentation strains: from the cradle to CRISPR/Cas9. . J. Ind. Microbiol. Biotechnol. 45::1003–6
     [Crossref] [Google Scholar]
  5. 5.
    Bedford E, Tabor S, Richardson CC. 1997.. The thioredoxin binding domain of bacteriophage T7 DNA polymerase confers processivity on Escherichia coli DNA polymerase I. . Biochemistry 94::479–84
     [Google Scholar]
  6. 6.
    Bonhivers M, Plançon L, Ghazi A, Boulanger P, le Maire M, et al. 1998.. FhuA, an Escherichia coli outer membrane protein with a dual function of transporter and channel which mediates the transport of phage DNA. . Biochimie 80::363–69
     [Crossref] [Google Scholar]
  7. 7.
    Boyer HW. 1971.. DNA restriction and modification mechanisms in bacteria. . Annu. Rev. Microbiol. 25::153–76
     [Crossref] [Google Scholar]
  8. 8.
    Bukovska G, Klucar L, Vlcek C, Adamovic J, Turna J, Timko J. 2006.. Complete nucleotide sequence and genome analysis of bacteriophage BFK20—a lytic phage of the industrial producer Brevibacterium flavum. . Virology 348::57–71
     [Crossref] [Google Scholar]
  9. 9.
    Cao B, Chen C, DeMott MS, Cheng Q, Clark TA, et al. 2014.. Genomic mapping of phosphorothioates reveals partial modification of short consensus sequences. . Nat. Commun. 5::3951
     [Crossref] [Google Scholar]
  10. 10.
    Cao B, Cheng Q, Gu C, Yao F, DeMott MS, et al. 2014.. Pathological phenotypes and in vivoDNA cleavage by unrestrained activity of a phosphorothioate-based restriction system in Salmonella. . Mol. Microbiol. 93::776–85
     [Crossref] [Google Scholar]
  11. 11.
    Chen C, Wang L, Chen S, Wu X, Gu M, et al. 2017.. Convergence of DNA methylation and phosphorothioation epigenetics in bacterial genomes. . PNAS 114::4501–6
     [Crossref] [Google Scholar]
  12. 12.
    Cheng R, Huang F, Lu X, Yan Y, Yu B, et al. 2023.. Prokaryotic Gabija complex senses and executes nucleotide depletion and DNA cleavage for antiviral defense. . Cell Host Microbe 31::1331–44
     [Crossref] [Google Scholar]
  13. 13.
    Cao B, Wu X, Zhou J, Wu H, Liu L, et al. 2020.. Nick-seq for single-nucleotide resolution genomic maps of DNA modifications and damage. . Nucleic Acids Res. 48::6715–25
     [Crossref] [Google Scholar]
  14. 14.
    Doron S, Melamed S, Ofir G, Leavitt A, Lopatina A, et al. 2018.. Systematic discovery of antiphage defense systems in the microbial pangenome. . Science 359::eaar4120
     [Crossref] [Google Scholar]
  15. 15.
    Eckstein F. 2014.. Phosphorothioates, essential components of therapeutic oligonucleotides. . Nucleic Acid Ther. 24::374–87
     [Crossref] [Google Scholar]
  16. 16.
    Gan R, Wu X, He W, Liu Z, Wu S, et al. 2014.. DNA phosphorothioate modifications influence the global transcriptional response and protect DNA from double-stranded breaks. . Sci. Rep. 4::6642
     [Crossref] [Google Scholar]
  17. 17.
    Gao H, Gong X, Zhou J, Zhang Y, Duan J, et al. 2022.. Nicking mechanism underlying the DNA phosphorothioate-sensing antiphage defense by SspE. . Nat. Commun. 13::6773
     [Crossref] [Google Scholar]
  18. 18.
    Gao L, Altae-Tran H, Böhning F, Makarova KS, Segel M, et al. 2020.. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. . Science 369::1077–84
     [Crossref] [Google Scholar]
  19. 19.
    Garneau JE, Moineau S. 2011.. Bacteriophages of lactic acid bacteria and their impact on milk fermentations. . Microb. Cell Fact. 10:(Suppl. 1):S20
     [Crossref] [Google Scholar]
  20. 20.
    Gordeeva J, Morozova N, Sierro N, Isaev A, Sinkunas T, et al. 2019.. BREX system of Escherichia coli distinguishes self from non-self by methylation of a specific DNA site. . Nucleic Acids. Res. 47::253–65
     [Crossref] [Google Scholar]
  21. 21.
    Han T, Yamada-Mabuchi M, Zhao G, Li L, Liu G, et al. 2015.. Recognition and cleavage of 5-methylcytosine DNA by bacterial SRA-HNH proteins. . Nucleic Acids. Res. 43::1147–59
     [Crossref] [Google Scholar]
  22. 22.
    Handa N, Kobayashi I. 1999.. Post-segregational killing by restriction modification gene complexes: observations of individual cell deaths. . Biochimie 81::931−38
     [Crossref] [Google Scholar]
  23. 23.
    He W, Huang T, Tang Y, Liu Y, Wu X, et al. 2015.. Regulation of DNA phosphorothioate modification in Salmonella enterica by DndB. . Sci. Rep. 5::12368
     [Crossref] [Google Scholar]
  24. 24.
    Hidese R, Mihara H, Esaki N. 2011.. Bacterial cysteine desulfurases: versatile key players in biosynthetic pathways of sulfur-containing biofactors. . Appl. Microbiol. Biotechnol. 91::47–61
     [Crossref] [Google Scholar]
  25. 25.
    Hobbs SJ, Wein T, Lu A, Morehouse BR, Schnabel J, et al. 2022.. Phage anti-CBASS and anti-Pycsar nucleases subvert bacterial immunity. . Nature 605::522–26
     [Crossref] [Google Scholar]
  26. 26.
    Hu W, Yang B, Xiao Q, Wang Y, Shuai Y, et al. 2023.. Characterization of a promiscuous DNA sulfur binding domain and application in site-directed RNA base editing. . Nucleic Acids Res. 51::10782–94
     [Crossref] [Google Scholar]
  27. 27.
    Hyjek-Składanowska M, Anderson BA, Mykhaylyk V, Orr C, Wagner A, et al. 2023.. Structures of annexin A2-PS DNA complexes show dominance of hydrophobic interactions in phosphorothioate binding. . Nucleic Acids Res. 51::1409–23
     [Crossref] [Google Scholar]
  28. 28.
    Jablonska J, Matelska D, Steczkiewicz K, Ginalski K. 2017.. Systematic classification of the His-Me finger superfamily. . Nucleic Acids Res. 45::11479–94
     [Crossref] [Google Scholar]
  29. 29.
    Kambampati R, Lauhon CT. 2000.. Evidence for the transfer of sulfane sulfur from IscS to ThiI during the in vitro biosynthesis of 4-thiouridine in Escherichia coli tRNA. . J. Biol. Chem. 275::10727–30
     [Crossref] [Google Scholar]
  30. 30.
    Koonin EV, Makarova KS, Wolf YI. 2017.. Evolutionary genomics of defense systems in archaea and bacteria. . Annu. Rev. Microbiol. 71::233–61
     [Crossref] [Google Scholar]
  31. 31.
    Yamasaki K, Akutsu Y, Yamasaki T, Miyagishi M, Kubota T. 2020.. Enhanced affinity of racemic phosphorothioate DNA with transcription factor SATB1 arising from diastereomer-specific hydrogen bonds and hydrophobic contacts. . Nucleic Acids Res. 48::4551–61
     [Crossref] [Google Scholar]
  32. 32.
    Kuttan A, Bass BL. 2012.. Mechanistic insights into editing-site specificity of ADARs. . PNAS 109::19521
     [Crossref] [Google Scholar]
  33. 33.
    Lacks SA, Mannarelii BM, Springhorn SS, Greenberg B. 1986.. Genetic basis of the complemental Dpnl and Dpnll restriction systems of S. pneumoniae: an intercellular cassette mechanism. . Cell 46::993–1000
     [Crossref] [Google Scholar]
  34. 34.
    Liang X-H, Shen W, Sun H, Kinberger GA, Prakash TP, et al. 2016.. Hsp90 protein interacts with phosphorothioate oligonucleotides containing hydrophobic 2′-modifications and enhances antisense activity. . Nucleic Acids Res. 44::3892–907
     [Crossref] [Google Scholar]
  35. 35.
    Liu G, Ou H-Y, Wang T, Li L, Tan H, et al. 2010.. Cleavage of phosphorothioated DNA and methylated DNA by the type IV restriction endonuclease ScoMcrA. . PLOS Genet. 6::e1001253
     [Crossref] [Google Scholar]
  36. 36.
    Liu G, Fu W, Zhang Z, He Y, Yu H, et al. 2018.. Structural basis for the recognition of sulfur in phosphorothioated DNA. . Nat. Commun. 9::4689
     [Crossref] [Google Scholar]
  37. 37.
    Liu L, Jiang S, Xing M, Chen C, Lai C, et al. 2020.. Structural analysis of an l-cysteine desulfurase from an Ssp DNA phosphorothioation system. . mBio 11::e00488-20
     [Google Scholar]
  38. 38.
    Los M. 2012.. Minimization and prevention of phage infections in bioprocesses. . In Microbial Metabolic Engineering, ed. Q Cheng , pp. 305–15. Methods Mol. Biol . New York:: Springer
     [Google Scholar]
  39. 39.
    Lowey B, Whiteley AT, Keszei AFA, Morehouse BR, Mathews IT, et al. 2020.. CBASS immunity uses CARF-related effectors to sense 3′–5′- and 2′–5′-linked cyclic oligonucleotide signals and protect bacteria from phage infection. . Cell 182::38–49
     [Crossref] [Google Scholar]
  40. 40.
    Lu Z, Pérez-Díaz IM, Hayes JS, Breidt F. 2012.. Bacteriophage ecology in a commercial cucumber fermentation. . Appl. Environ. Microbiol. 78::8571–78
     [Crossref] [Google Scholar]
  41. 41.
    Machnicka MA, Kaminska KH, Dunin-Horkawicz S, Bujnicki JM. 2015.. Phylogenomics and sequence-structure-function relationships in the GmrSD family of type IV restriction enzymes. . BMC Bioinform. 16::336
     [Crossref] [Google Scholar]
  42. 42.
    Millman A, Melamed S, Amitai G, Sorek R. 2020.. Diversity and classification of cyclic-oligonucleotide-based anti-phage signalling systems. . Nat. Microbiol. 5::1608–15
     [Crossref] [Google Scholar]
  43. 43.
    Murphy J, Royer B, Mahony J, Hoyles L, Heller K, et al. 2013.. Biodiversity of lactococcal bacteriophages isolated from 3 Gouda-type cheese-producing plants. . J. Dairy Sci. 96::4945–57
     [Crossref] [Google Scholar]
  44. 44.
    Pu T, Liang J, Mei Z, Deng Z, Wang Z. 2019.. Phosphorothioated DNA is shielded from oxidative damage. . Appl. Environ. Microbiol. 85::e00104-19
     [Crossref] [Google Scholar]
  45. 45.
    Rajakumara E, Nakarakanti NK, Nivya MA, Satish M. 2016.. Mechanistic insights into the recognition of 5-methylcytosine oxidation derivatives by the SUVH5 SRA domain. . Sci. Rep. 6::20161
     [Crossref] [Google Scholar]
  46. 46.
    Schüler MA, Stegmann BA, Poehlein A, Daniel R, Dürre P. 2020.. Genome sequence analysis of the temperate bacteriophage TBP2 of the solvent producer Clostridium saccharoperbutylacetonicum N1-4 (HMT, ATCC 27021). . FEMS Microbiol. Lett. 367::fnaa103
     [Crossref] [Google Scholar]
  47. 47.
    Shen J, Zhou J, Fu H, Mu Y, Sun Y, et al. 2016.. A Klebsiella pneumoniae bacteriophage and its effect on 1,3-propanediol fermentation. . Process Biochem. 51::1323–30
     [Crossref] [Google Scholar]
  48. 48.
    Shuai Y, Ju Y, Li Y, Ma D, Jiang L, et al. 2023.. A rapid nucleic acid detection platform based on phosphorothioate-DNA and sulfur binding domain. . Synth. Syst. Biotechnol. 8::213–19
     [Crossref] [Google Scholar]
  49. 49.
    Stokar-Avihail A, Fedorenko T, Hör J, Garb J, Leavitt A, et al. 2023.. Discovery of phage determinants that confer sensitivity to bacterial immune systems. . Cell 186::1863–76
     [Crossref] [Google Scholar]
  50. 50.
    Tal N, Morehouse BR, Millman A, Stokar-Avihail A, Avraham C, et al. 2021.. Cyclic CMP and cyclic UMP mediate bacterial immunity against phages. . Cell 184::5728–39.e16
     [Crossref] [Google Scholar]
  51. 51.
    Tong T, Chen S, Wang L, Tang Y, Ryu JY, et al. 2018.. Occurrence, evolution, and functions of DNA phosphorothioate epigenetics in bacteria. . PNAS 115::E2988–96
     [Crossref] [Google Scholar]
  52. 52.
    Vogel P, Stafforst T. 2019.. Critical review on engineering deaminases for site-directed RNA editing. . Curr. Opin. Biotechnol. 55::74–80
     [Crossref] [Google Scholar]
  53. 53.
    Wang L, Chen S, Vergin KL, Giovannoni SJ, Chan SW, et al. 2011.. DNA phosphorothioation is widespread and quantized in bacterial genomes. . PNAS 108::2963–8
     [Crossref] [Google Scholar]
  54. 54.
    Wang L, Chen S, Xu T, Taghizadeh K, Wishnok JS, et al. 2007.. Phosphorothioation of DNA in bacteria by dnd genes. . Nat. Chem. Biol. 3::709–10
     [Crossref] [Google Scholar]
  55. 55.
    Wang L, Jiang S, Deng Z, Dedon PC, Chen S. 2018.. DNA phosphorothioate modification—a new multi-functional epigenetic system in bacteria. . FEMS Microbiol. Rev. 43::109–22
     [Crossref] [Google Scholar]
  56. 56.
    Wang S, Wan M, Huang R, Zhang Y, Xie Y, et al. 2021.. SspABCD-SspFGH constitutes a new type of DNA phosphorothioate-based bacterial defense system. . mBio 12::e00613-21
     [Google Scholar]
  57. 57.
    Wei Y, Huang Q, Tian X, Zhang M, He J, et al. 2021.. Single-molecule optical mapping of the distribution of DNA phosphorothioate epigenetics. . Nucleic Acids Res. 49::3672–80
     [Crossref] [Google Scholar]
  58. 58.
    Wiegand T, Karambelkar S, Bondy-Denomy J, Wiedenheft B. 2020.. Structures and strategies of anti-CRISPR-mediated immune suppression. . Annu. Rev. Microbiol. 74::21–37
     [Crossref] [Google Scholar]
  59. 59.
    Wu D, Tang Y, Chen S, He Y, Chang X, et al. 2022.. The functional coupling between restriction and DNA phosphorothioate modification systems underlying the DndFGH restriction complex. . Nat. Catal. 5::1131–44
     [Crossref] [Google Scholar]
  60. 60.
    Wu X, Cao B, Aquino P, Chiu T-P, Chen C, et al. 2020.. Epigenetic competition reveals density-dependent regulation and target site plasticity of phosphorothioate epigenetics in bacteria. . PNAS 117::14322–30
     [Crossref] [Google Scholar]
  61. 61.
    Xia S, Chen J, Liu L, Wei Y, Deng Z, et al. 2019.. Tight control of genomic phosphorothioate modification by the ATP-modulated autoregulation and reusability of DndB. . Mol. Microbiol. 111::938–50
     [Crossref] [Google Scholar]
  62. 62.
    Xiong L, Liu S, Chen S, Xiao Y, Zhu B, et al. 2019.. A new type of DNA phosphorothioation-based antiviral system in archaea. . Nat. Commun. 10::1688
     [Crossref] [Google Scholar]
  63. 63.
    Xiong W, Zhao G, Yu H, He X. 2015.. Interactions of Dnd proteins involved in bacterial DNA phosphorothioate modification. . Front. Microbiol. 6::1139
     [Google Scholar]
  64. 64.
    Xiong X, Wu G, Wei Y, Liu L, Zhang Y, et al. 2020.. SspABCD–SspE is a phosphorothioation-sensing bacterial defence system with broad anti-phage activities. . Nat. Microbiol. 5::917–28
     [Crossref] [Google Scholar]
  65. 65.
    Xu S-y, Corvaglia AR, Chan S-H, Zheng Y, Linder P. 2011.. A type IV modification-dependent restriction enzyme SauUSI from Staphylococcus aureus subsp. aureus USA300. . Nucleic Acids Res. 39::5597–610
     [Crossref] [Google Scholar]
  66. 66.
    Xu T, Yao F, Zhou X, Deng Z, You D. 2010.. A novel host-specific restriction system associated with DNA backbone S-modification in Salmonella. . Nucleic Acids Res. 38::7133–41
     [Crossref] [Google Scholar]
  67. 67.
    Yao F, Xu T, Zhou X, Deng Z, You D. 2009.. Functional analysis of spfD gene involved in DNA phosphorothioation in Pseudomonas fluorescens Pf0–1. . FEBS Lett. 583::729–33
     [Crossref] [Google Scholar]
  68. 68.
    You D, Wang L, Yao F, Zhou X, Deng Z. 2007.. A novel DNA modification by sulfur: DndA is a NifS-like cysteine desulfurase capable of assembling DndC as an iron-sulfur cluster protein in Streptomyces lividans. . Biochemistry 46::6126–33
     [Crossref] [Google Scholar]
  69. 69.
    Yu H, Liu G, Zhao G, Hu W, Wu G, et al. 2018.. Identification of a conserved DNA sulfur recognition domain by characterizing the phosphorothioate-specific endonuclease SprMcrA from Streptomyces pristinaespiralis. . Mol. Microbiol. 110::484–97
     [Crossref] [Google Scholar]
  70. 70.
    Yuan B-F. 2019.. Assessment of DNA epigenetic modifications. . Chem. Res. Toxicol. 33::695–708
     [Crossref] [Google Scholar]
  71. 71.
    Yuan X, Huang Z, Zhu Z, Zhang J, Wu Q, et al. 2023.. Recent advances in phage defense systems and potential overcoming strategies. . Biotechnol. Adv. 65::108152
     [Crossref] [Google Scholar]
  72. 72.
    Zhou T, Xiong J, Wang M, Yang N, Wong J, et al. 2014.. Structural basis for hydroxymethylcytosine recognition by the SRA domain of UHRF2. . Mol. Cell 54::879–86
     [Crossref] [Google Scholar]
  73. 73.
    Zhou X, He X, Liang J, Li A, Xu T, et al. 2005.. A novel DNA modification by sulphur. . Mol. Microbiol. 57::1428–38
     [Crossref] [Google Scholar]
  74. 74.
    Zhu S, Zheng T, Kong L, Li J, Cao B, et al. 2020.. Development of methods derived from iodine-induced specific cleavage for identification and quantitation of DNA phosphorothioate modifications. . Biomolecules 10::1491
     [Crossref] [Google Scholar]
  75. 75.
    Zou X, Xiao X, Mo Z, Ge Y, Jiang X, et al. 2022.. Systematic strategies for developing phage resistant Escherichia coli strains. . Nat. Commun. 13::4491
     [Crossref] [Google Scholar]
/content/journals/10.1146/annurev-micro-041222-014330
Loading
DNA Phosphorothioate Modification Systems and Associated Phage Defense Systems
Annual Review of Microbiology 78, 447 (2024); https://doi.org/10.1146/annurev-micro-041222-014330
/content/journals/10.1146/annurev-micro-041222-014330
/content/journals/10.1146/annurev-micro-041222-014330
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error