Evolutionary stability of collateral sensitivity to antibiotics in the model pathogen Pseudomonas aeruginosa

Abstract
Data availability
Article and author information
Metrics

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.

The following data sets were generated

(2019) Evolutionary stability of antibiotic collateral sensitivity
NCBI Bioproject, PRJNA524114.

https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA524114

Article and author information

Author details

Camilo Barbosa

Department of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany

Competing interests
The authors declare that no competing interests exist.
Roderich Römhild

Department of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany

Competing interests
The authors declare that no competing interests exist.
Philip Rosenstiel

Institute of Clinical Molecular Biology, University of Kiel, Kiel, Germany

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9692-8828
Hinrich Schulenburg

Department of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany

For correspondence
hschulenburg@zoologie.uni-kiel.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1413-913X

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.

Copyright

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.