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

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.

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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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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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