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Phage–Antibiotic Synergy Inhibited by Temperate and Chronic Virus Competition

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Abstract

As antibiotic resistance grows more frequent for common bacterial infections, alternative treatment strategies such as phage therapy have become more widely studied in the medical field. While many studies have explored the efficacy of antibiotics, phage therapy, or synergistic combinations of phages and antibiotics, the impact of virus competition on the efficacy of antibiotic treatment has not yet been considered. Here, we model the synergy between antibiotics and two viral types, temperate and chronic, in controlling bacterial infections. We demonstrate that while combinations of antibiotic and temperate viruses exhibit synergy, competition between temperate and chronic viruses inhibits bacterial control with antibiotics. In fact, our model reveals that antibiotic treatment may counterintuitively increase the bacterial load when a large fraction of the bacteria are antibiotic resistant, and both chronic and temperate phages are present.

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Data Availability

All software (MATLAB .m files) are publicly available via the Illinois Data Bank (https://doi.org/10.13012/B2IDB-9460305_V1).

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Acknowledgements

The authors thank Jayadevi H. Chandrashekhar and George A. O’Toole for discussions that informed biological aspects of this work. Thanks are also due to Ted Kim and Karna Gowda for assistance with parameter selection. The authors also thank Laura Suttenfield, Alan Collins, and two anonymous reviewers for suggestions that greatly improved the clarity of the paper.

Funding

This work was funded in part by the National Science Foundation grant DMS-1815764 (ZR), the Cystic Fibrosis Foundation grant WHITAK16PO (RJW), and an Allen Distinguished Investigator Award (RJW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Mathematics, Statistics, and Computer Science, St. Olaf College, Northfield, MN, 55057, USA

    Kylie J. Landa, Lauren M. Mossman & Sara M. Clifton

  2. Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Rachel J. Whitaker

  3. Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Rachel J. Whitaker & Zoi Rapti

  4. Department of Mathematics, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Zoi Rapti

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  1. Kylie J. Landa
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Landa, K.J., Mossman, L.M., Whitaker, R.J. et al. Phage–Antibiotic Synergy Inhibited by Temperate and Chronic Virus Competition. Bull Math Biol 84, 54 (2022). https://doi.org/10.1007/s11538-022-01006-6

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