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Tackling antibiotic resistance by inducing transient and robust collateral sensitivity

Author

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  • Sara Hernando-Amado

    (Centro Nacional de Biotecnología, CSIC)

  • Pablo Laborda

    (Centro Nacional de Biotecnología, CSIC
    Technical University of Denmark
    Rigshospitalet)

  • José Luis Martínez

    (Centro Nacional de Biotecnología, CSIC)

Abstract

Collateral sensitivity (CS) is an evolutionary trade-off traditionally linked to the mutational acquisition of antibiotic resistance (AR). However, AR can be temporally induced, and the possibility that this causes transient, non-inherited CS, has not been addressed. Mutational acquisition of ciprofloxacin resistance leads to robust CS to tobramycin in pre-existing antibiotic-resistant mutants of Pseudomonas aeruginosa. Further, the strength of this phenotype is higher when nfxB mutants, over-producing the efflux pump MexCD-OprJ, are selected. Here, we induce transient nfxB-mediated ciprofloxacin resistance by using the antiseptic dequalinium chloride. Notably, non-inherited induction of AR renders transient tobramycin CS in the analyzed antibiotic-resistant mutants and clinical isolates, including tobramycin-resistant isolates. Further, by combining tobramycin with dequalinium chloride we drive these strains to extinction. Our results support that transient CS could allow the design of new evolutionary strategies to tackle antibiotic-resistant infections, avoiding the acquisition of AR mutations on which inherited CS depends.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37357-4
    DOI: 10.1038/s41467-023-37357-4
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    References listed on IDEAS

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    1. Daniel Nichol & Joseph Rutter & Christopher Bryant & Andrea M. Hujer & Sai Lek & Mark D. Adams & Peter Jeavons & Alexander R. A. Anderson & Robert A. Bonomo & Jacob G. Scott, 2019. "Antibiotic collateral sensitivity is contingent on the repeatability of evolution," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    2. Viktória Lázár & István Nagy & Réka Spohn & Bálint Csörgő & Ádám Györkei & Ákos Nyerges & Balázs Horváth & Andrea Vörös & Róbert Busa-Fekete & Mónika Hrtyan & Balázs Bogos & Orsolya Méhi & Gergely Fek, 2014. "Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network," Nature Communications, Nature, vol. 5(1), pages 1-12, September.
    3. 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.
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