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Suppressing evolution of antibiotic resistance through environmental switching

Theoretical Ecology volume 15, pages 115–127 (2022)Cite this article

Abstract

Ecology and evolution under changing environments are important in many subfields of biology with implications for medicine. Here, we explore an example: the consequences of fluctuating environments on the emergence of antibiotic resistance, which is an immense and growing problem. Typically, high doses of antibiotics are employed to eliminate the infection quickly and minimize the time under which resistance may emerge. However, this strategy may not be optimal. Since competition can reduce fitness and resistance typically has a reproductive cost, resistant mutants’ fitness can depend on their environment. Here we show conditions under which environmental varying fitness can be exploited to prevent the emergence of resistance. We develop a stochastic Lotka-Volterra model of a microbial system with competing phenotypes: a wild strain susceptible to the antibiotic, and a mutant strain that is resistant. We investigate the impact of various pulsed applications of antibiotics on population suppression. Leveraging competition, we show how a strategy of environmental switching can suppress the infection while avoiding resistant mutants. We discuss limitations of the procedure depending on the microbe and pharmacodynamics and methods to ameliorate them.

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Availability of data and material

Not applicable.

Code availability

The code to run the numerical simulations are available at https://github.com/bmorsky/antibioticresistance.

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Acknowledgements

We would like to thank Plamen Kamenov and Giuseppe Forte for assistance with earlier versions of this project.

Funding

This material is based upon work supported by the Defense Advanced Research Projects Agency under Contract No. HR0011-16-C-0062, and the University of Pennsylvania.

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Authors and Affiliations

  1. Department of Physics, University of Notre Dame, Nieuwland Science Hall, Notre Dame, IN, USA

    Bryce Morsky & Dervis Can Vural

  2. Department of Biology, University of Pennsylvania, Carolyn Lynch Laboratories, Philadelphia, PA, USA

    Bryce Morsky

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  1. Bryce Morsky
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  2. Dervis Can Vural
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Both authors contributed to the conception of the study and the final manuscript. B.M. developed the code for and analyzed the numerical simulations, and wrote the first draft.

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Correspondence to Bryce Morsky.

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Morsky, B., Vural, D.C. Suppressing evolution of antibiotic resistance through environmental switching. Theor Ecol 15, 115–127 (2022). https://doi.org/10.1007/s12080-022-00530-4

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Keywords

  • Antibiotic resistance
  • Changing environments
  • Competition
  • Lotka-Volterra
  • Microbial ecology
  • Pulsed antibiotic treatment