Article

The unconstrained evolution of fast and efficient antibiotic-resistant bacterial genomes

  • Nature Ecology & Evolution 1, Article number: 0050 (2017)
  • doi:10.1038/s41559-016-0050
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Abstract

Evolutionary trajectories are constrained by trade-offs when mutations that benefit one life history trait incur fitness costs in other traits. As resistance to tetracycline antibiotics by increased efflux can be associated with an increase in length of the Escherichia coli chromosome of 10% or more, we sought costs of resistance associated with doxycycline. However, it was difficult to identify any because the growth rate (r), carrying capacity (K) and drug efflux rate of E. coli increased during evolutionary experiments where the species was exposed to doxycycline. Moreover, these improvements remained following drug withdrawal. We sought mechanisms for this seemingly unconstrained adaptation, particularly as these traits ought to trade-off according to rK selection theory. Using prokaryote and eukaryote microorganisms, including clinical pathogens, we show that r and K can trade-off, but need not, because of ‘rK trade-ups’. r and K trade-off only in sufficiently carbon-rich environments where growth is inefficient. We then used E. coli ribosomal RNA (rRNA) knockouts to determine specific mutations, namely changes in rRNA operon (rrn) copy number, than can simultaneously maximize r and K. The optimal genome has fewer operons, and therefore fewer functional ribosomes, than the ancestral strain. It is, therefore, unsurprising for r-adaptation in the presence of a ribosome-inhibiting antibiotic, doxycycline, to also increase population size. We found two costs for this improvement: an elongated lag phase and the loss of stress protection genes.

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Acknowledgements

The rrn knockout strains derived from E. coli MG1655 were gifted by T. Bollenbach, strain AG100 was provided by S. Levy and Candida strains were a gift from S. Bates, who are sincerely thanked for their help.

Author information

Author notes

    • Mark Hewlett
    •  & Sarah Duxbury

    These authors contributed equally to this work.

Affiliations

  1. Biosciences, Geoffrey Pope, University of Exeter, Stocker Road, Exeter EX4 4QD, UK

    • Carlos Reding-Roman
    • , Mark Hewlett
    • , Sarah Duxbury
    • , Fabio Gori
    • , Ivana Gudelj
    •  & Robert Beardmore

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Contributions

R.B., I.G., M.H. and C.R.R. proposed research questions and hypotheses, and subsequently designed the experiments; R.B., C.R.R., F.G. and M.H. designed and wrote computer codes to analyse the data; C.R.R., M.H. and S.D. performed the experiments; and R.B., C.R.R. and I.G. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Robert Beardmore.

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    Supplementary information

    Supplementary Figures 1–15; Supplementary Tables 1,2