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A competitive trade-off limits the selective advantage of increased antibiotic production

Nature Microbiology volume 1, Article number: 16175 (2016) | Download Citation

Abstract

In structured environments, antibiotic-producing microorganisms can gain a selective advantage by inhibiting nearby competing species1. However, despite their genetic potential2,3, natural isolates often make only small amounts of antibiotics, and laboratory evolution can lead to loss rather than enhancement of antibiotic production4. Here, we show that, due to competition with antibiotic-resistant cheater cells, increased levels of antibiotic production can actually decrease the selective advantage to producers. Competing fluorescently labelled Escherichia coli colicin producers with non-producing resistant and sensitive strains on solid media, we found that although producer colonies can greatly benefit from the inhibition of nearby sensitive colonies, this benefit is shared with resistant colonies growing in their vicinity. A simple model, which accounts for such local competitive and inhibitory interactions, suggests that the advantage of producers varies non-monotonically with the amount of production. Indeed, experimentally varying the amount of production shows a peak in selection for producers, reflecting a trade-off between benefit gained by inhibiting sensitive competitors and loss due to an increased contribution to resistant cheater colonies. These results help explain the low level of antibiotic production observed for natural species and can help direct laboratory evolution experiments selecting for increased or novel production of antibiotics.

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Acknowledgements

The authors thank E. Kelsic, A. Palmer and M. Elowitz for comments on the manuscript and E. Toprak for providing the colicin strains. Y.G. acknowledges support from the Hertz Foundation and the National Science Foundation (NSF) Graduate Research Fellowship. M.K. acknowledges support from NSF grant no. 1349248. R.K. acknowledges the support of the European Research Council Seventh Framework Programme (ERC grant no. 281891), the National Institutes of Health (grant no. R01GM081617) and the Israeli Centers of Research Excellence I-CORE Program (ISF grant no. 152/11).

Author information

Affiliations

  1. Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA

    • Ylaine Gerardin
    •  & Michael Springer
  2. Faculty of Biology and Faculty of Computer Science, Technion – Israel Institute of Technology, Haifa 3200003, Israel

    • Roy Kishony

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Contributions

Y.G., M.S. and R.K. designed the study. Y.G. performed experiments and analysis. Y.G., M.S. and R.K. interpreted the results and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Michael Springer or Roy Kishony.

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    Supplementary Figures 1–12, Supplementary Table 1

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DOI

https://doi.org/10.1038/nmicrobiol.2016.175

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