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Phage–host population dynamics promotes prophage acquisition in bacteria with innate immunity

Nature Ecology & Evolution volume 2, pages 359–366 (2018)Cite this article

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Abstract

Temperate bacteriophages integrate in bacterial genomes as prophages and represent an important source of genetic variation for bacterial evolution, frequently transmitting fitness-augmenting genes such as toxins responsible for virulence of major pathogens. However, only a fraction of bacteriophage infections are lysogenic and lead to prophage acquisition, whereas the majority are lytic and kill the infected bacteria. Unless able to discriminate lytic from lysogenic infections, mechanisms of immunity to bacteriophages are expected to act as a double-edged sword and increase the odds of survival at the cost of depriving bacteria of potentially beneficial prophages. We show that although restriction–modification systems as mechanisms of innate immunity prevent both lytic and lysogenic infections indiscriminately in individual bacteria, they increase the number of prophage-acquiring individuals at the population level. We find that this counterintuitive result is a consequence of phage–host population dynamics, in which restriction–modification systems delay infection onset until bacteria reach densities at which the probability of lysogeny increases. These results underscore the importance of population-level dynamics as a key factor modulating costs and benefits of immunity to temperate bacteriophages.

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Fig. 1: RM systems represent a barrier to prophage acquisition in individual bacteria.
Fig. 2: RM systems increase the number of prophage-acquiring bacteria at the population level.
Fig. 3: RM systems promote prophage acquisition on a population level under a wide range of initial conditions.
Fig. 4: RM systems delay the onset of infection and increase the probability of lysogeny.
Fig. 5: Delay in the onset of infection increases the probability of prophage acquisition.

References

  1. Wilson, G. G. & Murray, N. E. Restriction and modification systems. Annu. Rev. Genet. 25, 585–627 (1991).

    Article  CAS  PubMed  Google Scholar 

  2. Vasu, K. & Nagaraja, V. Diverse functions of restriction–modification systems in addition to cellular defense. Microbiol. Mol. Biol. Rev. 77, 53–72 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Oliveira, P. H., Touchon, M. & Rocha, E. P. C. The interplay of restriction–modification systems with mobile genetic elements and their prokaryotic hosts. Nucleic Acids Res. 42, 10618–10631 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Murray, N. E. Immigration control of DNA in bacteria: self versus non-self. Microbiology 148, 3–20 (2002).

    Article  CAS  PubMed  Google Scholar 

  5. Abedon, S. T. Bacterial ‘immunity’ against bacteriophages. Bacteriophage 2, 50–54 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Tock, M. R. & Dryden, D. T. F. The biology of restriction and anti-restriction. Curr. Opin. Microbiol.. 8, 466–472 (2005).

    Article  CAS  PubMed  Google Scholar 

  7. Lwoff, A. Lysogeny. Bacteriol. Rev. 17, 269–337 (1953).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Bobay, L.-M., Rocha, E. P. C. & Touchon, M. The adaptation of temperate bacteriophages to their host genomes. Mol. Biol. Evol. 30, 737–751 (2013).

    Article  CAS  PubMed  Google Scholar 

  9. Casjens, S. Prophages and bacterial genomics: what have we learned so far? Mol. Microbiol. 49, 277–300 (2003).

    Article  CAS  PubMed  Google Scholar 

  10. Lin, L., Bitner, R. & Edlin, G. Increased reproductive fitness of Escherichia coli lambda lysogens. J. Virol. 21, 554–559 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Edlin, G., Lin, L. & Bitner, R. Reproductive fitness of P1, P2, and Mu lysogens of Escherichia coli. J. Virol. 21, 560–564 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Oliver, K., Degnan, P., Hunter, M. & Moran, N. Bacteriophages encode factors required for protection in a symbiotic mutualism. Science 325, 992–994 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Obeng, N., Pratama, A. A. & Elsas, J. D. The significance of mutualistic phages for bacterial ecology and evolution. Trends Microbiol. 24, 440–449 (2016).

    Article  CAS  PubMed  Google Scholar 

  14. O’Brien, A. D. et al. Shiga-like toxin-converting phages from Escherichia coli strains that cause hemorrhagic colitis or infantile diarrhea. Science 226, 694–696 (1984).

    Article  PubMed  Google Scholar 

  15. Barondess, J. J. & Beckwith, J. A bacterial virulence determinant encoded by lysogenic coliphage λ. Nature 346, 871–874 (1990).

    Article  CAS  PubMed  Google Scholar 

  16. Waldor, M. & Mekalanos, J. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 272, 1910–1914 (1996).

    Article  CAS  PubMed  Google Scholar 

  17. Brüssow, H., Canchaya, C., Hardt, W. & Bru, H. Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion. Microbiol. Mol. Biol. Rev. 68, 560–602 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wang, X. et al. Cryptic prophages help bacteria cope with adverse environments. Nat. Commun. 1, 147 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Rice, S. A. et al. The biofilm life cycle and virulence of Pseudomonas aeruginosa are dependent on a filamentous prophage. ISME J. 3, 271–282 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. Bondy-Denomy, J. et al. Prophages mediate defense against phage infection through diverse mechanisms. ISME J. 22, 1–13 (2016).

    Google Scholar 

  21. Brown, S. P., Le Chat, L., De Paepe, M. & Taddei, F. Ecology of microbial invasions: amplification allows virus carriers to invade more rapidly when rare. Curr. Biol. 16, 2048–2052 (2006).

    Article  CAS  PubMed  Google Scholar 

  22. Davies, E. V. et al. Temperate phages both mediate and drive adaptive evolution in pathogen biofilms. Proc. Natl. Acad. Sci. USA 113, 8266–8271 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Barrangou, R. et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science 315, 1709–1712 (2007).

    Article  CAS  PubMed  Google Scholar 

  24. Goldberg, G. W., Jiang, W., Bikard, D. & Marraffini, L. A. Conditional tolerance of temperate phages via transcription-dependent CRISPR-Cas targeting. Nature 514, 633–637 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Edgar, R. & Qimron, U. The Escherichia coli CRISPR system protects from λ lysogenization, lysogens, and prophage induction. J. Bacteriol. 192, 6291–6294 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Roberts, R. A nomenclature for restriction enzymes, DNA methyltransferases, homing endonucleases and their genes. Nucleic Acids Res. 31, 1805–1812 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Pleška, M. et al. Bacterial autoimmunity due to a restriction–modification system. Curr. Biol. 26, 404–409 (2016).

    Article  PubMed  Google Scholar 

  28. St-Pierre, F. & Endy, D. Determination of cell fate selection during phage lambda infection. Proc. Natl. Acad. Sci. USA 105, 20705–20710 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hong, J.-S., Smith, G. R. & Ames, B. N. Adenosine 3′:5′-cyclic monophosphate concentration in the bacterial host regulates the viral decision between lysogeny and lysis. Proc. Natl. Acad. Sci. USA 68, 2258–2262 (1971).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Deveau, H. et al. Phage response to CRISPR-encoded resistance in Streptococcus thermophilus. J. Bacteriol. 190, 1390–1400 (2008).

    Article  CAS  PubMed  Google Scholar 

  31. Houte, Svan et al. The diversity-generating benefits of a prokaryotic adaptive immune system. Nature 532, 385–388 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Touchon, M., Bernheim, A. & Rocha, E. P. Genetic and life-history traits associated with the distribution of prophages in bacteria. ISME J. 10, 1–11 (2016).

    Article  Google Scholar 

  33. Clokie, M. R., Millard, A. D., Letarov, A. V. & Heaphy, S. Phages in nature. Bacteriophage 1, 31–45 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Canchaya, C., Fournous, G., Chibani-Chennoufi, S., Dillmann, M. L. & Brüssow, H. Phage as agents of lateral gene transfer. Curr. Opin. Microbiol. 6, 417–424 (2003).

    Article  CAS  PubMed  Google Scholar 

  35. Ochman, H., Lawrence, J. G. & Groisman, E. A. Lateral gene transfer and the nature of bacterial innovation. Nature 405, 299–304 (2000).

    Article  CAS  PubMed  Google Scholar 

  36. Lieb, M. The establishment of lysogenicity in Escherichia coli. J. Bacteriol. 65, 642–651 (1953).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Kourilsky, P. Lysogenization by bacteriophage lambda. MGG Mol. Gen. Genet.. 122, 183–195 (1973).

    Article  CAS  PubMed  Google Scholar 

  38. Zeng, L. et al. Decision making at a subcellular level determines the outcome of bacteriophage infection. Cell 141, 682–691 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Akerlund, T., Nordström, K. & Bernander, R. Analysis of cell size and DNA content in exponentially growing and stationary-phase batch cultures of Escherichia coli. J. Bacteriol. 177, 6791–6797 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Knowles, B. et al. Lytic to temperate switching of viral communities. Nature 531, 466–470 (2016).

    Article  CAS  PubMed  Google Scholar 

  41. Knowles, B. et al. Variability and host density independence in inductions-based estimates of environmental lysogeny. Nat. Microbiol.. 2, 17064 (2017).

    Article  CAS  PubMed  Google Scholar 

  42. Erez, Z. et al. Communication between viruses guides lysis–lysogeny decisions. Nature 541, 488–493 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Gandon, S. Why be temperate: lessons from bacteriophage λ. Trends Microbiol.. 24, 356–365 (2016).

    Article  CAS  PubMed  Google Scholar 

  44. Oliveira, P. H., Touchon, M. & Rocha, E. P. C. Regulation of genetic flux between bacteria by restriction–modification systems. Proc. Natl. Acad. Sci. USA 113, 5658–5663 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Naito, T., Kusano, K. & Kobayashi, I. Selfish behavior of restriction–modification systems. Science 267, 897–899 (1995).

    Article  CAS  PubMed  Google Scholar 

  46. Rocha, E. P. C., Danchin, A. & Viari, A. Evolutionary role of restriction–modification systems as revealed by comparative genome analysis. Genome Res. 11, 946–958 (2001).

    Article  CAS  PubMed  Google Scholar 

  47. Lenski, R. E. & Levin, B. R. Constraints on the coevolution of bacteria and virulent phage: a model, some experiments, and predictions for natural communities. Am. Nat. 125, 585–602 (1985).

    Article  Google Scholar 

  48. Korona, R. & Levin, B. Phage-mediated selection and the evolution and maintenance of restriction–modification. Evolution 47, 556–575 (1993).

    Article  PubMed  Google Scholar 

  49. Levin, B. R., Moineau, S., Bushman, M. & Barrangou, R. The population and evolutionary dynamics of phage and bacteria with CRISPR-mediated immunity. PLoS. Genet. 9, e1003312 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Westra, E. R. et al. Parasite exposure drives selective evolution of constitutive versus inducible defense. Curr. Biol. 25, 1043–1049 (2015).

    Article  CAS  PubMed  Google Scholar 

  51. Stewart, F. M. & Levin, B. R. The population biology of bacterial viruses: why be temperate. Theor. Popul. Biol. 26, 93–117 (1984).

    Article  CAS  PubMed  Google Scholar 

  52. Ripp, S. & Miller, R. V. The role of pseudolysogeny in bacteriophage–host interactions in a natural freshwater environment. Microbiology 143, 2065–2070 (1997).

    Article  CAS  Google Scholar 

  53. Takahashi, N., Naito, Y., Handa, N. & Kobayashi, I. A DNA methyltransferase can protect the genome from postdisturbance attack by a restriction–modification gene complex. J. Bacteriol. 184, 6100–6108 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Blumenthal, R. M., Gregory, S. A. & Cooperider, J. S. Cloning of a restriction–modification system from Proteus vulgaris and its use in analyzing a methylase-sensitive phenotype in Escherichia coli. J. Bacteriol. 164, 501–509 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was funded by an HFSP Young Investigators’ grant (C.C.G.) and a grant from the United States National Institutes of Health (GM 091875) (B.R.L.). M.P. is a recipient of a DOC Fellowship of the Austrian Academy of Science at the Institute of Science and Technology Austria. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA Grant Agreement No. 291734. We wish to thank A. Bagwatt, R. Blumenthal, I. Kobayashi, S. Makovets, S. Moineau, I. Mruk and M. Szczelkun for providing us with RM plasmids and phages. We thank S. Abedon, N. Balaban, D. Siekhaus, G. Tkacik and members of the C.C.G. laboratory for in-depth discussions and comments on the manuscript. We especially thank V. Krishna KV for assistance with the experiments.

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Authors and Affiliations

  1. Institute of Science and Technology Austria, Am Campus 1, Klosterneuburg, Austria

    Maroš Pleška, Moritz Lang & Călin C. Guet

  2. Zurich University of Applied Sciences, Campus Grüental, Wädenswil, Switzerland

    Dominik Refardt

  3. Department of Biology, Emory University, Atlanta, GA, USA

    Bruce R. Levin

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  1. Maroš Pleška
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Contributions

C.C.G., B.R.L. and M.P. designed the research, M.P. performed the experiments and analysed data, D.R. constructed the λ kan phage, M.L. and M.P. constructed and analysed the model, and C.C.G., B.R.L., M.L. and M.P. wrote the paper.

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Correspondence to Călin C. Guet.

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Pleška, M., Lang, M., Refardt, D. et al. Phage–host population dynamics promotes prophage acquisition in bacteria with innate immunity. Nat Ecol Evol 2, 359–366 (2018). https://doi.org/10.1038/s41559-017-0424-z

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