IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-49122-2.html
   My bibliography  Save this article

β-lactamase expression induces collateral sensitivity in Escherichia coli

Author

Listed:
  • Cristina Herencias

    (Hospital Universitario Ramón y Cajal
    Instituto de Salud Carlos III)

  • Laura Álvaro-Llorente

    (Hospital Universitario Ramón y Cajal)

  • Paula Ramiro-Martínez

    (Hospital Universitario Ramón y Cajal)

  • Ariadna Fernández-Calvet

    (Centro Nacional de Biotecnología-CSIC)

  • Ada Muñoz-Cazalla

    (Hospital Universitario Ramón y Cajal)

  • Javier DelaFuente

    (Centro Nacional de Biotecnología-CSIC)

  • Fabrice E. Graf

    (University of Gothenburg
    University of Gothenburg
    Liverpool School of Tropical Medicine)

  • Laura Jaraba-Soto

    (Hospital Universitario Ramón y Cajal)

  • Juan Antonio Castillo-Polo

    (Hospital Universitario Ramón y Cajal)

  • Rafael Cantón

    (Hospital Universitario Ramón y Cajal
    Instituto de Salud Carlos III)

  • Álvaro San Millán

    (Centro Nacional de Biotecnología-CSIC
    Instituto de Salud Carlos III)

  • Jerónimo Rodríguez-Beltrán

    (Hospital Universitario Ramón y Cajal
    Instituto de Salud Carlos III)

Abstract

Major antibiotic groups are losing effectiveness due to the uncontrollable spread of antimicrobial resistance (AMR) genes. Among these, β-lactam resistance genes –encoding β-lactamases– stand as the most common resistance mechanism in Enterobacterales due to their frequent association with mobile genetic elements. In this context, novel approaches that counter mobile AMR are urgently needed. Collateral sensitivity (CS) occurs when the acquisition of resistance to one antibiotic increases susceptibility to another antibiotic and can be exploited to eliminate AMR selectively. However, most CS networks described so far emerge as a consequence of chromosomal mutations and cannot be leveraged to tackle mobile AMR. Here, we dissect the CS response elicited by the acquisition of a prevalent antibiotic resistance plasmid to reveal that the expression of the β-lactamase gene blaOXA-48 induces CS to colistin and azithromycin. We next show that other clinically relevant mobile β-lactamases produce similar CS responses in multiple, phylogenetically unrelated E. coli strains. Finally, by combining experiments with surveillance data comprising thousands of antibiotic susceptibility tests, we show that β-lactamase-induced CS is pervasive within Enterobacterales. These results highlight that the physiological side-effects of β-lactamases can be leveraged therapeutically, paving the way for the rational design of specific therapies to block mobile AMR or at least counteract their effects.

Suggested Citation

  • Cristina Herencias & Laura Álvaro-Llorente & Paula Ramiro-Martínez & Ariadna Fernández-Calvet & Ada Muñoz-Cazalla & Javier DelaFuente & Fabrice E. Graf & Laura Jaraba-Soto & Juan Antonio Castillo-Polo, 2024. "β-lactamase expression induces collateral sensitivity in Escherichia coli," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49122-2
    DOI: 10.1038/s41467-024-49122-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-49122-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-49122-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. Ana Rita Brochado & Anja Telzerow & Jacob Bobonis & Manuel Banzhaf & André Mateus & Joel Selkrig & Emily Huth & Stefan Bassler & Jordi Zamarreño Beas & Matylda Zietek & Natalie Ng & Sunniva Foerster &, 2018. "Species-specific activity of antibacterial drug combinations," Nature, Nature, vol. 559(7713), pages 259-263, July.
    3. 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.
    4. Ian B. Seiple & Ziyang Zhang & Pavol Jakubec & Audrey Langlois-Mercier & Peter M. Wright & Daniel T. Hog & Kazuo Yabu & Senkara Rao Allu & Takehiro Fukuzaki & Peter N. Carlsen & Yoshiaki Kitamura & Xi, 2016. "A platform for the discovery of new macrolide antibiotics," Nature, Nature, vol. 533(7603), pages 338-345, May.
    5. Carolina López & Juan A. Ayala & Robert A. Bonomo & Lisandro J. González & Alejandro J. Vila, 2019. "Protein determinants of dissemination and host specificity of metallo-β-lactamases," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    6. Mislav Acman & Ruobing Wang & Lucy Dorp & Liam P. Shaw & Qi Wang & Nina Luhmann & Yuyao Yin & Shijun Sun & Hongbin Chen & Hui Wang & Francois Balloux, 2022. "Role of mobile genetic elements in the global dissemination of the carbapenem resistance gene blaNDM," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    7. Anaïs Eskenazi & Cédric Lood & Julia Wubbolts & Maya Hites & Nana Balarjishvili & Lika Leshkasheli & Lia Askilashvili & Leila Kvachadze & Vera Noort & Jeroen Wagemans & Marc Jayankura & Nina Chanishvi, 2022. "Combination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    8. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. 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.
    2. Teemu Kuosmanen & Johannes Cairns & Robert Noble & Niko Beerenwinkel & Tommi Mononen & Ville Mustonen, 2021. "Drug-induced resistance evolution necessitates less aggressive treatment," PLOS Computational Biology, Public Library of Science, vol. 17(9), pages 1-22, September.
    3. Dimitri Boeckaerts & Michiel Stock & Celia Ferriol-González & Jesús Oteo-Iglesias & Rafael Sanjuán & Pilar Domingo-Calap & Bernard Baets & Yves Briers, 2024. "Prediction of Klebsiella phage-host specificity at the strain level," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    4. Christopher J. Barden & Fan Wu & J. Pedro Fernandez-Murray & Erhu Lu & Shengguo Sun & Marcia M. Taylor & Annette L. Rushton & Jason Williams & Mahtab Tavasoli & Autumn Meek & Alla Siva Reddy & Lisa M., 2024. "Computer-aided drug design to generate a unique antibiotic family," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    5. Nunes E. L. C. & Novais J. S. & Silva A. C. J. A. & Guerra L. R. & Castro H. C., 2017. "The Future is Still Ahead: Methodologies for Discovering New Antimicrobials within the World Biodiversity," Journal of Biotechnology Research, Academic Research Publishing Group, vol. 3(1), pages 1-9, 01-2017.
    6. Yiqing Wang & Tal Dagan, 2024. "The evolution of antibiotic resistance islands occurs within the framework of plasmid lineages," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Chih-Wei Chen & Nadja Leimer & Egor A. Syroegin & Clémence Dunand & Zackery P. Bulman & Kim Lewis & Yury S. Polikanov & Maxim S. Svetlov, 2023. "Structural insights into the mechanism of overcoming Erm-mediated resistance by macrolides acting together with hygromycin-A," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Daniel P. Newton & Po-Yi Ho & Kerwyn Casey Huang, 2023. "Modulation of antibiotic effects on microbial communities by resource competition," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    9. 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.
    10. 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.
    11. Xiaokang Lv & Fen Su & Hongyan Long & Fengfei Lu & Yukun Zeng & Minghong Liao & Fengrui Che & Xingxing Wu & Yonggui Robin Chi, 2024. "Carbene organic catalytic planar enantioselective macrolactonization," Nature Communications, Nature, vol. 15(1), pages 1-7, December.
    12. 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.
    13. Darryl M. Wilson & Daniel J. Driedger & Dennis Y. Liu & Sandra Keerthisinghe & Adrian Hermann & Christoph Bieniossek & Roger G. Linington & Robert A. Britton, 2024. "Targeted sampling of natural product space to identify bioactive natural product-like polyketide macrolides," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    14. Neythen J Treloar & Alex J H Fedorec & Brian Ingalls & Chris P Barnes, 2020. "Deep reinforcement learning for the control of microbial co-cultures in bioreactors," PLOS Computational Biology, Public Library of Science, vol. 16(4), pages 1-18, April.
    15. Fabian Kunisch & Claudia Campobasso & Jeroen Wagemans & Selma Yildirim & Benjamin K. Chan & Christoph Schaudinn & Rob Lavigne & Paul E. Turner & Michael J. Raschke & Andrej Trampuz & Mercedes Gonzalez, 2024. "Targeting Pseudomonas aeruginosa biofilm with an evolutionary trained bacteriophage cocktail exploiting phage resistance trade-offs," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    16. Sebastián Serna-Loaiza & Angela Miltner & Martin Miltner & Anton Friedl, 2019. "A Review on the Feedstocks for the Sustainable Production of Bioactive Compounds in Biorefineries," Sustainability, MDPI, vol. 11(23), pages 1-24, November.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49122-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.