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Translating eco-evolutionary biology into therapy to tackle antibiotic resistance

Nature Reviews Microbiology volume 21, pages 671–685 (2023)Cite this article

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Abstract

Antibiotic resistance is currently one of the most important public health problems. The golden age of antibiotic discovery ended decades ago, and new approaches are urgently needed. Therefore, preserving the efficacy of the antibiotics currently in use and developing compounds and strategies that specifically target antibiotic-resistant pathogens is critical. The identification of robust trends of antibiotic resistance evolution and of its associated trade-offs, such as collateral sensitivity or fitness costs, is invaluable for the design of rational evolution-based, ecology-based treatment approaches. In this Review, we discuss these evolutionary trade-offs and how such knowledge can aid in informing combination or alternating antibiotic therapies against bacterial infections. In addition, we discuss how targeting bacterial metabolism can enhance drug activity and impair antibiotic resistance evolution. Finally, we explore how an improved understanding of the original physiological function of antibiotic resistance determinants, which have evolved to reach clinical resistance after a process of historical contingency, may help to tackle antibiotic resistance.

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Fig. 1: Natural selection and random drift in the evolution of antibiotic resistance.
Fig. 2: Exploitable trade-offs of antibiotic resistance evolution.
Fig. 3: Methodologies to detect robust evolutionary trade-offs associated with antibiotic resistance and therapeutic strategies based on these robust patterns.
Fig. 4: Examples of bacterial metabolic changes that impair antimicrobial resistance.
Fig. 5: Interfering with the activity of efflux pumps to impair bacterial virulence.

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Acknowledgements

Work in the authors’ laboratories was supported by Ministerio de Ciencia e Innovación (MCIN), Agencia Estatal de Investigación (AEI) MCIN/AEI/10.13039/501100011033 grant PID2020-113521RB-I00. T.G.-G. is recipient of a Formación de Personal Investigador fellowship from Ministerio de Economía y Competitividad.

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Authors and Affiliations

  1. Departamento de Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, Zaragoza, Spain

    Fernando Sanz-García

  2. Centro Nacional de Biotecnología, CSIC, Darwin 3, Madrid, Spain

    Teresa Gil-Gil, Pablo Laborda, Luz-Edith Ochoa-Sánchez, José Luis Martínez & Sara Hernando-Amado

  3. Programa de Doctorado en Biociencias Moleculares, Universidad Autónoma de Madrid, Madrid, Spain

    Teresa Gil-Gil

  4. The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark

    Pablo Laborda

  5. Department of Clinical Microbiology, 9301, Rigshospitalet, Copenhagen, Denmark

    Pablo Laborda

  6. Molecular Basis of Adaptation, Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain

    Paula Blanco

  7. VISAVET Health Surveillance Centre, Universidad Complutense Madrid, Madrid, Spain

    Paula Blanco

  8. Department of Microbiology, Hospital Universitario Ramón y Cajal (IRYCIS), CIBER en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

    Fernando Baquero

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Contributions

J.L.M., S.H.-A., F.S.-G. and F.B. contributed substantially to the discussion of the content. J.L.M, T.G.-G., S.H.-A., P.L., L.-E.O.-S., P.B., F.S.-G. and F.B. wrote the article. J.L.M, T.G.-G., S.H.-A., P.L., L.-E.O.-S., P.B., F.S.-G. and F.B. reviewed and edited the manuscript before submission.

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Correspondence to José Luis Martínez or Sara Hernando-Amado.

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Sanz-García, F., Gil-Gil, T., Laborda, P. et al. Translating eco-evolutionary biology into therapy to tackle antibiotic resistance. Nat Rev Microbiol 21, 671–685 (2023). https://doi.org/10.1038/s41579-023-00902-5

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