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Conserved collateral antibiotic susceptibility networks in diverse clinical strains of Escherichia coli

Author

Listed:
  • Nicole L. Podnecky

    (UiT The Arctic University of Norway)

  • Elizabeth G. A. Fredheim

    (UiT The Arctic University of Norway)

  • Julia Kloos

    (UiT The Arctic University of Norway)

  • Vidar Sørum

    (UiT The Arctic University of Norway)

  • Raul Primicerio

    (UiT The Arctic University of Norway)

  • Adam P. Roberts

    (Liverpool School of Tropical Medicine
    Liverpool School of Tropical Medicine)

  • Daniel E. Rozen

    (Leiden University)

  • Ørjan Samuelsen

    (UiT The Arctic University of Norway
    University Hospital of North Norway)

  • Pål J. Johnsen

    (UiT The Arctic University of Norway)

Abstract

There is urgent need to develop novel treatment strategies to reduce antimicrobial resistance. Collateral sensitivity (CS), where resistance to one antimicrobial increases susceptibility to other drugs, might enable selection against resistance during treatment. However, the success of this approach would depend on the conservation of CS networks across genetically diverse bacterial strains. Here, we examine CS conservation across diverse Escherichia coli strains isolated from urinary tract infections. We determine collateral susceptibilities of mutants resistant to relevant antimicrobials against 16 antibiotics. Multivariate statistical analyses show that resistance mechanisms, in particular efflux-related mutations, as well as the relative fitness of resistant strains, are principal contributors to collateral responses. Moreover, collateral responses shift the mutant selection window, suggesting that CS-informed therapies may affect evolutionary trajectories of antimicrobial resistance. Our data allow optimism for CS-informed therapy and further suggest that rapid detection of resistance mechanisms is important to accurately predict collateral responses.

Suggested Citation

  • Nicole L. Podnecky & Elizabeth G. A. Fredheim & Julia Kloos & Vidar Sørum & Raul Primicerio & Adam P. Roberts & Daniel E. Rozen & Ørjan Samuelsen & Pål J. Johnsen, 2018. "Conserved collateral antibiotic susceptibility networks in diverse clinical strains of Escherichia coli," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06143-y
    DOI: 10.1038/s41467-018-06143-y
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    Cited by:

    1. Jeff Maltas & Kevin B Wood, 2019. "Pervasive and diverse collateral sensitivity profiles inform optimal strategies to limit antibiotic resistance," PLOS Biology, Public Library of Science, vol. 17(10), pages 1-34, October.
    2. Shraddha Karve & Andreas Wagner, 2022. "Environmental complexity is more important than mutation in driving the evolution of latent novel traits in E. coli," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Natalie J. E. Waller & Chen-Yi Cheung & Gregory M. Cook & Matthew B. McNeil, 2023. "The evolution of antibiotic resistance is associated with collateral drug phenotypes in Mycobacterium tuberculosis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Sara Hernando-Amado & Pablo Laborda & José Luis Martínez, 2023. "Tackling antibiotic resistance by inducing transient and robust collateral sensitivity," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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