Evolutionary stability of collateral sensitivity to antibiotics in the model pathogen Pseudomonas aeruginosa
- University of Kiel, Germany
Abstract
Evolution is at the core of the impending antibiotic crisis. Sustainable therapy must thus account for the adaptive potential of pathogens. One option is to exploit evolutionary trade-offs, like collateral sensitivity, where evolved resistance to one antibiotic causes hypersensitivity to another one. To date, the evolutionary stability and thus clinical utility of this trade-off is unclear. We performed a critical experimental test on this key requirement, using evolution experiments with Pseudomonas aeruginosa, and identified three main outcomes: (i) bacteria commonly failed to counter hypersensitivity and went extinct; (ii) hypersensitivity sometimes converted into multidrug resistance; and (iii) resistance gains frequently caused re-sensitization to the previous drug, thereby maintaining the trade-off. Drug order affected the evolutionary outcome, most likely due to variation in the effect size of collateral sensitivity, epistasis among adaptive mutations, and fitness costs. Our finding of robust genetic trade-offs and drug-order effects can guide design of evolution-informed antibiotic therapy.
Data availability
Sequencing data have been deposited at NCBI under the BioProject number: PRJNA524114.All other data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all figures.
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Evolutionary stability of antibiotic collateral sensitivityNCBI Bioproject, PRJNA524114.
Article and author information
Author details
Hinrich Schulenburg
Funding
Deutsche Forschungsgemeinschaft (SCHU 1415/12-1)
- Hinrich Schulenburg
Deutsche Forschungsgemeinschaft (EXC 22167-39088401)
- Philip Rosenstiel
- Hinrich Schulenburg
Leibniz-Gemeinschaft (EvoLUNG)
- Camilo Barbosa
- Hinrich Schulenburg
Max-Planck-Gesellschaft (IMPRS Evolutionary Biology)
- Camilo Barbosa
- Roderich Römhild
Max-Planck-Gesellschaft (Fellowship)
- Hinrich Schulenburg
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Csaba Pal, Biological Research Centre of the Hungarian Academy of Sciences, Hungary
Version history
- Received: August 30, 2019
- Accepted: October 21, 2019
- Accepted Manuscript published: October 29, 2019 (version 1)
- Version of Record published: November 27, 2019 (version 2)
Copyright
© 2019, Barbosa et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Evolutionary stability of collateral sensitivity to antibiotics in the model pathogen Pseudomonas aeruginosa
eLife 8:e51481.
https://doi.org/10.7554/eLife.51481
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