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Cited by 174Evolution and Genetic DynamicsAntibiotic Resistance in BacteriaAntimicrobial Resistance in Staphylococcus

Antibiotic collateral sensitivity is contingent on the repeatability of evolution

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Nichol, Daniel, Rutter, Joseph, Bryant, Christopher, Hujer, Andrea M., Lek, Sai, Adams, Mark D., Jeavons, Peter, Anderson, Alexander R. A. +2 more·2019·Nature Communications
DOI 10.1038/s41467-018-08098-6PMC PMC6338734

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Abstract

Antibiotic resistance represents a growing health crisis that necessitates the immediate discovery of novel treatment strategies. One such strategy is the identification of collateral sensitivities, wherein evolution under a first drug induces susceptibility to a second. Here, we report that sequential drug regimens derived from in vitro evolution experiments may have overstated therapeutic benefit, predicting a collaterally sensitive response where cross-resistance ultimately occurs. We quantify the likelihood of this phenomenon by use of a mathematical model parametrised with combinatorially complete fitness landscapes for Escherichia coli. Through experimental evolution we then verify that a second drug can indeed stochastically exhibit either increased susceptibility or increased resistance when following a first. Genetic divergence is confirmed as the driver of this differential response through targeted and whole genome sequencing. Taken together, these results highlight that the success of evolutionarily-informed therapies is predicated on a rigorous probabilistic understanding of the contingencies that arise during the evolution of drug resistance.

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Cited by

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Authors
Nichol, D., Rutter, J., Bryant, C., Hujer, A. M., Lek, S., Adams, M. D., Jeavons, P., Anderson, A. R. A., Bonomo, R. A., & Scott, J. G.
Affiliations
  • Institute of Cancer Research (GB)
  • Louis Stokes Cleveland VA Medical Center (US)
  • The Jackson Laboratory for Genomic Medicine (US)
  • University of Oxford (GB)
  • Moffitt Cancer Center (US)
  • Cleveland Clinic (US)
Corresponding author
  • Nichol, Daniel
  • Scott, Jacob G.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-01-18
Volume
10
Issue
1
Pages
334-334
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-018-08098-6
PMC
PMC6338734
OpenAlex
W2908913542
Cited by
174
References
2
Citations by year
2026: 16 · 2025: 15 · 2024: 26 · 2023: 25 · 2022: 22 · 2021: 27 · 2020: 27 · 2019: 15 · 2018: 1
FWCI
13.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
Funders
  • U.S. Department of Veterans Affairs (I01 BX001974, 1I01BX001974)
  • Office of Research and Development (1I01BX001974, VISN 10)
  • National Institutes of Health (R01AI100560, R01AI063517, and R01AI072219, R01AI100560, R01AI063517, NIH K12CA076917)
  • Geriatric Research Education and Clinical Center (VISN 10))
  • Engineering and Physical Sciences Research Council
  • National Cancer Institute (U54CA193489, K12CA076917, NIH K12CA076917)
  • National Institute of Allergy and Infectious Diseases (R01AI100560, R01AI063517, and R01AI072219, R01AI100560, R01AI063517, and, R01AI063517, R01AI100560, R01AI072219)
  • NIH Clinical Center
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
  • Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
Keywords
collateral sensitivity, antibiotic resistance, cross-resistance, fitness landscape, Escherichia coli, experimental evolution, genetic divergence
MeSH terms
Whole Genome Sequencing, Anti-Bacterial Agents, Cefotaxime, Drug Resistance, Microbial, Escherichia coli, Genotype, Microbial Sensitivity Tests, Models, Genetic, Models, Theoretical, Mutation, Genome, Bacterial, Evolution, Molecular, Gene Expression Profiling, Drug Resistance, Bacterial, Drug Resistance, Multiple, Bacterial, Genetic Fitness

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