The roles of history, chance, and natural selection in the evolution of antibiotic resistance
- University of Pittsburgh, United States
- Marquette University, United States
- Loyola University, United States
- Carnegie Mellon University, United States
Abstract
History, chance, and selection are the fundamental factors that drive and constrain evolution. We designed evolution experiments to disentangle and quantify effects of these forces on the evolution of antibiotic resistance. Previously we showed that selection of the pathogen Acinetobacter baumannii in both structured and unstructured environments containing the antibiotic ciprofloxacin produced distinct genotypes and phenotypes, with lower resistance in biofilms as well as collateral sensitivity to b-lactam drugs (Santos-Lopez et al. 2019). Here we study how this prior history influences subsequent evolution in new b-lactam antibiotics. Selection was imposed by increasing concentrations of ceftazidime and imipenem and chance differences arose as random mutations among replicate populations. The effects of history were reduced by increasingly strong selection in new drugs, but not erased, at times revealing important contingencies. A history of selection in structured environments constrained resistance to new drugs and led to frequent loss of resistance to the initial drug by genetic reversions and not compensatory mutations. This research demonstrates that despite strong selective pressures of antibiotics leading to genetic parallelism, history can etch potential vulnerabilities to orthogonal drugs.
Data availability
All data generated or analyzed in this study are included in the manuscript, supporting files, or at https://github.com/sirmicrobe/chance_history_selection, where raw experimental values and statistical analysis code is shared. All sequences were deposited into NCBI under the BioProject number PRJNA485123 and accession numbers can be found in Supplemental Table S2
Article and author information
Author details
Alfonso Santos-Lopez
Funding
National Institutes of Health (U01AI124302)
- Vaughn S Cooper
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- María Mercedes Zambrano, CorpoGen, Colombia
Version history
- Preprint posted: July 22, 2020 (view preprint)
- Received: June 1, 2021
- Accepted: August 24, 2021
- Accepted Manuscript published: August 25, 2021 (version 1)
- Version of Record published: September 2, 2021 (version 2)
Copyright
© 2021, Santos-Lopez 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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The roles of history, chance, and natural selection in the evolution of antibiotic resistance
eLife 10:e70676.
https://doi.org/10.7554/eLife.70676
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