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Using ecological coexistence theory to understand antibiotic resistance and microbial competition

Nature Ecology & Evolution volume 5, pages 431–441 (2021)Cite this article

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Abstract

Tackling antibiotic resistance necessitates deep understanding of how resource competition within and between species modulates the fitness of resistant microbes. Recent advances in ecological coexistence theory offer a powerful framework to probe the mechanisms regulating intra- and interspecific competition, but the significance of this body of theory to the problem of antibiotic resistance has been largely overlooked. In this Perspective, we draw on emerging ecological theory to illustrate how changes in resource niche overlap can be equally important as changes in competitive ability for understanding costs of resistance and the persistence of resistant pathogens in microbial communities. We then show how different temporal patterns of resource and antibiotic supply, alongside trade-offs in competitive ability at high and low resource concentrations, can have diametrically opposing consequences for the coexistence and exclusion of resistant and susceptible strains. These insights highlight numerous opportunities for innovative experimental and theoretical research into the ecological dimensions of antibiotic resistance.

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Fig. 1: Partitioning costs of resistance mediated by constraints on resource uptake into competitive ability differences and niche overlap.
Fig. 2: Partitioning costs of resistance mediated by constraints on resource uptake into competitive ability differences and niche overlap.
Fig. 3: The effect of constant versus pulsed delivery of a growth-inhibiting antibiotic on coexistence between a susceptible strain (blue) and a resistant mutant (green).
Fig. 4: Coexistence and exclusion of a susceptible and resistant strain across antibiotic pulse intervals of increasing length but the same time-averaged concentration, and decreasing costs of resistance.
Fig. 5: Simulation results illustrating the interactive effects of antibiotic pulsing, resource pulse interval length and resource pulse size on competitive outcomes under different resource-uptake-associated costs of resistance (maximum growth trade-off in left panel; R* trade-off in right panel).

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Acknowledgements

We thank D. McLeod, S. Bonhoeffer and the Pathogen Ecology group at ETH for thoughtful discussions and comments on an earlier draft of this manuscript. This project received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skodowska-Curie grant agreement no. 750779.

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  1. School of Biological Sciences, University of Queensland, Brisbane, Queensland, Australia

    Andrew D. Letten

  2. Department of Environmental Systems Science, Institute of Integrative Biology, ETH Zürich, Zürich, Switzerland

    Andrew D. Letten & Alex R. Hall

  3. Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA

    Jonathan M. Levine

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A.D.L., A.R.H. and J.M.L. conceived the study. A.D.L. performed simulations and analysis. A.D.L., A.R.H. and J.M.L. wrote the manuscript.

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Correspondence to Andrew D. Letten.

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Letten, A.D., Hall, A.R. & Levine, J.M. Using ecological coexistence theory to understand antibiotic resistance and microbial competition. Nat Ecol Evol 5, 431–441 (2021). https://doi.org/10.1038/s41559-020-01385-w

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