1887

Abstract

Phages are ubiquitous in nature, and bacteria with very different genomics, metabolisms, and lifestyles are subjected to their predation. Yet, the defence systems that allow bacteria to resist their phages have rarely been explored experimentally outside a very limited number of model organisms. Actinobacteria (Actinomycetota) are a phylum of GC-rich Gram-positive bacteria, which often produce an important diversity of secondary metabolites. Despite being ubiquitous in a wide range of environments, from soil to fresh and sea water but also the gut microbiome, relatively little is known about the anti-phage arsenal of Actinobacteria. In this work, we used DefenseFinder to systematically detect 131 anti-phage defence systems in 22803 fully sequenced prokaryotic genomes, among which are 2253 Actinobacteria of more than 700 species. We show that, like other bacteria, Actinobacteria encode many diverse anti-phage systems that are often encoded on mobile genetic elements. We further demonstrate that most detected defence systems are absent or rarer in Actinobacteria than in other bacteria, while a few rare systems are enriched (notably gp29-gp30 and Wadjet). We characterize the spatial distribution of anti-phage systems on chromosomes and show that some defence systems (e.g. RM systems) tend to be encoded in the core region, while others (e.g. Lamassu and Wadjet) are enriched towards the extremities. Overall, our results suggest that Actinobacteria might be a source of novel anti-phage systems and provide clues to characterize mechanistic aspects of known anti-phage systems.

Funding
This study was supported by the:
  • HORIZON EUROPE Framework Programme (Award 945298)
    • Principle Award Recipient: HelenaShomar
  • HORIZON EUROPE European Research Council (Award 101040529)
    • Principle Award Recipient: AudeBernheim
  • Inserm (Award R21042KS)
    • Principle Award Recipient: AudeBernheim
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. The Microbiology Society waived the open access fees for this article.
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.001374
2023-08-02
2024-04-29
Loading full text...

Full text loading...

/deliver/fulltext/micro/169/8/mic001374.html?itemId=/content/journal/micro/10.1099/mic.0.001374&mimeType=html&fmt=ahah

References

  1. Gao L, Altae-Tran H, Böhning F, Makarova KS, Segel M et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 2020; 369:1077–1084 [View Article] [PubMed]
    [Google Scholar]
  2. Doron S, Melamed S, Ofir G, Leavitt A, Lopatina A et al. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 2018; 359:eaar4120 [View Article] [PubMed]
    [Google Scholar]
  3. Vassallo CN, Doering CR, Littlehale ML, Teodoro GIC, Laub MT. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 2022; 7:1568–1579 [View Article] [PubMed]
    [Google Scholar]
  4. Rousset F, Depardieu F, Miele S, Dowding J, Laval A-L et al. Phages and their satellites encode hotspots of antiviral systems. Cell Host Microbe 2022; 30:740–753 [View Article] [PubMed]
    [Google Scholar]
  5. Flärdh K, Buttner MJ. Streptomyces morphogenetics: dissecting differentiation in a filamentous bacterium. Nat Rev Microbiol 2009; 7:36–49 [View Article] [PubMed]
    [Google Scholar]
  6. Barka EA, Vatsa P, Sanchez L, Gaveau-Vaillant N, Jacquard C et al. Taxonomy, physiology, and natural products of Actinobacteria. Microbiol Mol Biol Rev 2016; 80:1–43 [View Article] [PubMed]
    [Google Scholar]
  7. Hamedi J, Poorinmohammad N, Papiran R. Growth and life cycle of Actinobacteria. In Wink J, Mohammadipanah F, Hamedi J. eds Biology and Biotechnology of Actinobacteria Springer International Publishing; 2017 pp 29–50 [View Article]
    [Google Scholar]
  8. Gil F, Catalão MJ, Moniz-Pereira J, Leandro P, McNeil M et al. The lytic cassette of mycobacteriophage Ms6 encodes an enzyme with lipolytic activity. Microbiology 2008; 154:1364–1371 [View Article] [PubMed]
    [Google Scholar]
  9. Gil F, Grzegorzewicz AE, Catalão MJ, Vital J, McNeil MR et al. Mycobacteriophage Ms6 LysB specifically targets the outer membrane of Mycobacterium smegmatis. Microbiology 2010; 156:1497–1504 [View Article] [PubMed]
    [Google Scholar]
  10. Catalão MJ, Pimentel M. Mycobacteriophage lysis enzymes: targeting the Mycobacterial cell envelope. Viruses 2018; 10:428 [View Article] [PubMed]
    [Google Scholar]
  11. Demain AL, Sanchez S. Microbial drug discovery: 80 years of progress. J Antibiot 2009; 62:5–16 [View Article] [PubMed]
    [Google Scholar]
  12. Kirby R, Chen CW, Dyson P. Streptomyces: Molecular Biology and Biotechnology Norfolk: Caister Academic Press; 2011
    [Google Scholar]
  13. Bentley SD, Chater KF, Cerdeño-Tárraga A-M, Challis GL, Thomson NR et al. Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 2002; 417:141–147 [View Article] [PubMed]
    [Google Scholar]
  14. Choulet F, Gallois A, Aigle B, Mangenot S, Gerbaud C et al. Intraspecific variability of the terminal inverted repeats of the linear chromosome of Streptomyces ambofaciens. J Bacteriol 2006; 188:6599–6610 [View Article] [PubMed]
    [Google Scholar]
  15. Hatfull GF. Actinobacteriophages: genomics, dynamics, and applications. Annu Rev Virol 2020; 7:37–61 [View Article] [PubMed]
    [Google Scholar]
  16. Luthe T, Kever L, Hänsch S, Hardy A, Tschowri N et al. Streptomyces development is involved in the efficient containment of viral infections. Microlife 2023; 4:uqad002 [View Article] [PubMed]
    [Google Scholar]
  17. Kever L, Hardy A, Luthe T, Hünnefeld M, Gätgens C et al. Aminoglycoside antibiotics inhibit phage infection by blocking an early step of the infection cycle. mBio 2022; 13:e0078322 [View Article] [PubMed]
    [Google Scholar]
  18. Kronheim S, Daniel-Ivad M, Duan Z, Hwang S, Wong AI et al. A chemical defence against phage infection. Nature 2018; 564:283–286 [View Article] [PubMed]
    [Google Scholar]
  19. Tesson F, Hervé A, Mordret E, Touchon M, d’Humières C et al. Systematic and quantitative view of the antiviral arsenal of prokaryotes. Nat Commun 2022; 13:2561 [View Article] [PubMed]
    [Google Scholar]
  20. Medema MH, Blin K, Cimermancic P, de Jager V, Zakrzewski P et al. antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucleic Acids Res 2011; 39:W339–W346 [View Article] [PubMed]
    [Google Scholar]
  21. Roux S, Enault F, Hurwitz BL, Sullivan MB. VirSorter: mining viral signal from microbial genomic data. PeerJ 2015; 3:e985 [View Article] [PubMed]
    [Google Scholar]
  22. McKinney W. Data Structures for Statistical Computing in Python. In Python in Science Conference Austin, Texas: 2010 [View Article]
    [Google Scholar]
  23. Hunter JD. Matplotlib: A 2D graphics environment. Comput Sci Eng 2007; 9:90–95 [View Article]
    [Google Scholar]
  24. Waskom ML. seaborn: statistical data visualization. J Open Source Softw 2021; 6:3021 [View Article]
    [Google Scholar]
  25. Virtanen P, Gommers R, Oliphant TE, Haberland M, Reddy T et al. Author correction: SciPy 1.0: fundamental algorithms for scientific computing in Python. Nat Methods 2020; 17:352 [View Article] [PubMed]
    [Google Scholar]
  26. Seabold S, Perktold J. Statsmodels: econometric and statistical modeling with python. In Python in Science Conference Austin, Texas: 2010 [View Article]
    [Google Scholar]
  27. O’Leary NA, Wright MW, Brister JR, Ciufo S, Haddad D et al. Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. Nucleic Acids Res 2016; 44:D733–D745 [View Article] [PubMed]
    [Google Scholar]
  28. Perrin A, Rocha EPC. PanACoTA: a modular tool for massive microbial comparative genomics. NAR Genom Bioinform 2021; 3:lqaa106 [View Article] [PubMed]
    [Google Scholar]
  29. Letunic I, Bork P. Interactive Tree Of Life (iTOL): an online tool for phylogenetic tree display and annotation. Bioinformatics 2007; 23:127–128 [View Article] [PubMed]
    [Google Scholar]
  30. Revell LJ. phytools: an R package for phylogenetic comparative biology (and other things). Methods Ecol Evol 2012; 3:217–223 [View Article]
    [Google Scholar]
  31. Hampton HG, Watson BNJ, Fineran PC. The arms race between bacteria and their phage foes. Nature 2020; 577:327–336 [View Article] [PubMed]
    [Google Scholar]
  32. Bernheim A, Sorek R. The pan-immune system of bacteria: antiviral defence as a community resource. Nat Rev Microbiol 2020; 18:113–119 [View Article] [PubMed]
    [Google Scholar]
  33. Millman A, Melamed S, Leavitt A, Doron S, Bernheim A et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 2022; 30:1556–1569 [View Article] [PubMed]
    [Google Scholar]
  34. Deep A, Gu Y, Gao Y-Q, Ego KM, Herzik MA et al. The SMC-family Wadjet complex protects bacteria from plasmid transformation by recognition and cleavage of closed-circular DNA. Mol Cell 2022; 82:4145–4159 [View Article] [PubMed]
    [Google Scholar]
  35. Makarova KS, Wolf YI, Koonin EV. Comparative genomics of defense systems in archaea and bacteria. Nucleic Acids Res 2013; 41:4360–4377 [View Article] [PubMed]
    [Google Scholar]
  36. Fillol-Salom A, Rostøl JT, Ojiogu AD, Chen J, Douce G et al. Bacteriophages benefit from mobilizing pathogenicity islands encoding immune systems against competitors. Cell 2022; 185:3248–3262 [View Article] [PubMed]
    [Google Scholar]
  37. Hochhauser D, Millman A, Sorek R. The defence Island repertoire of the Escherichia coli. bioRxiv 2022 [View Article]
    [Google Scholar]
  38. LeGault KN, Hays SG, Angermeyer A, McKitterick AC, Johura F-T et al. Temporal shifts in antibiotic resistance elements govern phage-pathogen conflicts. Science 2021; 373:eabg2166 [View Article] [PubMed]
    [Google Scholar]
  39. Picton DM, Luyten YA, Morgan RD, Nelson A, Smith DL et al. The phage defence island of a multidrug resistant plasmid uses both BREX and type IV restriction for complementary protection from viruses. Nucleic Acids Res 2021; 49:11257–11273 [View Article] [PubMed]
    [Google Scholar]
  40. Yu YT, Snyder L. Translation elongation factor Tu cleaved by a phage-exclusion system. Proc Natl Acad Sci 1994; 91:802–806 [View Article] [PubMed]
    [Google Scholar]
  41. Puigbò P, Makarova KS, Kristensen DM, Wolf YI, Koonin EV. Reconstruction of the evolution of microbial defense systems. BMC Evol Biol 2017; 17:94 [View Article] [PubMed]
    [Google Scholar]
  42. Ravenhall M, Škunca N, Lassalle F, Dessimoz C. Inferring horizontal gene transfer. PLoS Comput Biol 2015; 11:e1004095 [View Article] [PubMed]
    [Google Scholar]
  43. Zhang R, Ou H-Y, Gao F, Luo H. Identification of horizontally-transferred genomic islands and genome segmentation points by using the GC profile method. Curr Genomics 2014; 15:113–121 [View Article]
    [Google Scholar]
  44. Gavriilidou A, Kautsar SA, Zaburannyi N, Krug D, Müller R et al. Compendium of specialized metabolite biosynthetic diversity encoded in bacterial genomes. Nat Microbiol 2022; 7:726–735 [View Article] [PubMed]
    [Google Scholar]
  45. Miao V, Davies J. Actinobacteria: the good, the bad, and the ugly. Antonie Van Leeuwenhoek 2010; 98:143–150 [View Article] [PubMed]
    [Google Scholar]
  46. Ziemert N, Lechner A, Wietz M, Millán-Aguiñaga N, Chavarria KL et al. Diversity and evolution of secondary metabolism in the marine actinomycete genus Salinispora. Proc Natl Acad Sci U S A 2014; 111:E1130–9 [View Article] [PubMed]
    [Google Scholar]
  47. McDonald BR, Currie CR. Lateral gene transfer dynamics in the ancient bacterial genus Streptomyces. mBio 2017; 8:e00644-17 [View Article] [PubMed]
    [Google Scholar]
  48. Aigle B, Lautru S, Spiteller D, Dickschat JS, Challis GL et al. Genome mining of Streptomyces ambofaciens. J Ind Microbiol Biotechnol 2014; 41:251–263 [View Article] [PubMed]
    [Google Scholar]
  49. Lioy VS, Lorenzi J-N, Najah S, Poinsignon T, Leh H et al. Dynamics of the compartmentalized Streptomyces chromosome during metabolic differentiation. Nat Commun 2021; 12:5221 [View Article] [PubMed]
    [Google Scholar]
  50. Lorenzi J-N, Lespinet O, Leblond P, Thibessard A. Subtelomeres are fast-evolving regions of the Streptomyces linear chromosome. Microb Genom 2019; 7:000525 [View Article] [PubMed]
    [Google Scholar]
  51. Xiong X, Wu G, Wei Y, Liu L, Zhang Y et al. SspABCD-SspE is a phosphorothioation-sensing bacterial defence system with broad anti-phage activities. Nat Microbiol 2020; 5:917–928 [View Article] [PubMed]
    [Google Scholar]
  52. Dedrick RM, Jacobs-Sera D, Bustamante CAG, Garlena RA, Mavrich TN et al. Prophage-mediated defence against viral attack and viral counter-defence. Nat Microbiol 2017; 2:16251 [View Article] [PubMed]
    [Google Scholar]
  53. Goldfarb T, Sberro H, Weinstock E, Cohen O, Doron S et al. BREX is a novel phage resistance system widespread in microbial genomes. EMBO J 2015; 34:169–183 [View Article] [PubMed]
    [Google Scholar]
  54. Sumby P, Smith MCM. Genetics of the phage growth limitation (Pgl) system of Streptomyces coelicolor A3(2). Mol Microbiol 2002; 44:489–500 [View Article] [PubMed]
    [Google Scholar]
  55. Mageeney CM, Mohammed HT, Dies M, Anbari S, Cudkevich N et al. Mycobacterium phage butters-encoded proteins contribute to host defense against viral attack. mSystems 2020; 5:e00534-20 [View Article] [PubMed]
    [Google Scholar]
  56. Gentile GM, Wetzel KS, Dedrick RM, Montgomery MT, Garlena RA et al. More evidence of collusion: a new prophage-mediated viral defense system encoded by Mycobacteriophage Sbash. mBio 2019; 10:e00196-19 [View Article] [PubMed]
    [Google Scholar]
  57. Mohammed HT, Mageeney C, Ware VC. Identification of a new antiphage system in Mycobacterium phage butters. bioRxiv 2023 [View Article]
    [Google Scholar]
  58. Russell DA, Hatfull GF. PhagesDB: the actinobacteriophage database. Bioinformatics 2017; 33:784–786 [View Article] [PubMed]
    [Google Scholar]
  59. Ongenae V, Mabrouk AS, Crooijmans M, Rozen D, Briegel A et al. Reversible bacteriophage resistance by shedding the bacterial cell wall. Open Biol 2022; 12:210379 [View Article] [PubMed]
    [Google Scholar]
  60. Karoonuthaisiri N, Weaver D, Huang J, Cohen SN, Kao CM. Regional organization of gene expression in Streptomyces coelicolor. Gene 2005; 353:53–66 [View Article] [PubMed]
    [Google Scholar]
  61. Lato DF, Golding GB. Spatial patterns of gene expression in bacterial genomes. J Mol Evol 2020; 88:510–520 [View Article] [PubMed]
    [Google Scholar]
  62. Liu HW, Roisné-Hamelin F, Beckert B, Li Y, Myasnikov A et al. DNA-measuring Wadjet SMC ATPases restrict smaller circular plasmids by DNA cleavage. Mol Cell 2022; 82:4727–4740 [View Article] [PubMed]
    [Google Scholar]
  63. Robins WP, Meader BT, Toska J, Mekalanos JJ. Cell density-dependent death triggered by viral palindromic DNA sequences. Microbiology 2022 [View Article]
    [Google Scholar]
  64. Hopwood DA. Soil to genomics: the Streptomyces chromosome. Annu Rev Genet 2006; 40:1–23 [View Article] [PubMed]
    [Google Scholar]
  65. Weaver D, Karoonuthaisiri N, Tsai H-H, Huang C-H, Ho M-L et al. Genome plasticity in Streptomyces: identification of 1 Mb TIRs in the S. coelicolor A3(2) chromosome. Mol Microbiol 2004; 51:1535–1550 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.001374
Loading
/content/journal/micro/10.1099/mic.0.001374
Loading

Data & Media loading...

Supplements

Supplementary material 1

EXCEL

Supplementary material 2

EXCEL

Supplementary material 3

EXCEL

Supplementary material 4

EXCEL

Supplementary material 5

PDF
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