IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39416-2.html
   My bibliography  Save this article

Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients

Author

Listed:
  • Julio Diaz Caballero

    (Department of Biology)

  • Rachel M. Wheatley

    (Department of Biology)

  • Natalia Kapel

    (Department of Biology)

  • Carla López-Causapé

    (Hospital Universitari Son Espases, Instituto de Investigación Sanitaria Illes Balears (IdISBa))

  • Thomas Van der Schalk

    (University of Antwerp)

  • Angus Quinn

    (Department of Biology)

  • Liam P. Shaw

    (Department of Biology)

  • Lois Ogunlana

    (Department of Biology)

  • Claudia Recanatini

    (University Medical Center Utrecht, Utrecht University)

  • Basil Britto Xavier

    (University of Antwerp)

  • Leen Timbermont

    (University of Antwerp)

  • Jan Kluytmans

    (University Medical Center Utrecht, Utrecht University)

  • Alexey Ruzin

    (BioPharmaceuticals R&D, AstraZeneca)

  • Mark Esser

    (BioPharmaceuticals R&D, AstraZeneca)

  • Surbhi Malhotra-Kumar

    (University of Antwerp)

  • Antonio Oliver

    (Hospital Universitari Son Espases, Instituto de Investigación Sanitaria Illes Balears (IdISBa))

  • R. Craig MacLean

    (Department of Biology)

Abstract

Antibiotic resistance poses a global health threat, but the within-host drivers of resistance remain poorly understood. Pathogen populations are often assumed to be clonal within hosts, and resistance is thought to emerge due to selection for de novo variants. Here we show that mixed strain populations are common in the opportunistic pathogen P. aeruginosa. Crucially, resistance evolves rapidly in patients colonized by multiple strains through selection for pre-existing resistant strains. In contrast, resistance evolves sporadically in patients colonized by single strains due to selection for novel resistance mutations. However, strong trade-offs between resistance and growth rate occur in mixed strain populations, suggesting that within-host diversity can also drive the loss of resistance in the absence of antibiotic treatment. In summary, we show that the within-host diversity of pathogen populations plays a key role in shaping the emergence of resistance in response to treatment.

Suggested Citation

  • Julio Diaz Caballero & Rachel M. Wheatley & Natalia Kapel & Carla López-Causapé & Thomas Van der Schalk & Angus Quinn & Liam P. Shaw & Lois Ogunlana & Claudia Recanatini & Basil Britto Xavier & Leen T, 2023. "Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39416-2
    DOI: 10.1038/s41467-023-39416-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39416-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39416-2?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. Hattie Chung & Christina Merakou & Matthew M. Schaefers & Kelly B. Flett & Sarah Martini & Roger Lu & Jennifer A. Blumenthal & Shanice S. Webster & Ashley R. Cross & Roy Al Ahmar & Erin Halpin & Miche, 2022. "Rapid expansion and extinction of antibiotic resistance mutations during treatment of acute bacterial respiratory infections," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. M. C. Bitter & L. Kapsenberg & J.-P. Gattuso & C. A. Pfister, 2019. "Standing genetic variation fuels rapid adaptation to ocean acidification," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    3. Rachel M. Wheatley & Julio Diaz Caballero & Thomas E. Schalk & Fien H. R. Winter & Liam P. Shaw & Natalia Kapel & Claudia Recanatini & Leen Timbermont & Jan Kluytmans & Mark Esser & Alicia Lacoma & Cr, 2022. "Gut to lung translocation and antibiotic mediated selection shape the dynamics of Pseudomonas aeruginosa in an ICU patient," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    4. A. San Millan & R. Peña-Miller & M. Toll-Riera & Z. V. Halbert & A. R. McLean & B. S. Cooper & R. C. MacLean, 2014. "Positive selection and compensatory adaptation interact to stabilize non-transmissible plasmids," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    5. Mel Greaves & Carlo C. Maley, 2012. "Clonal evolution in cancer," Nature, Nature, vol. 481(7381), pages 306-313, January.
    6. Felicity C. Jones & Manfred G. Grabherr & Yingguang Frank Chan & Pamela Russell & Evan Mauceli & Jeremy Johnson & Ross Swofford & Mono Pirun & Michael C. Zody & Simon White & Ewan Birney & Stephen Sea, 2012. "The genomic basis of adaptive evolution in threespine sticklebacks," Nature, Nature, vol. 484(7392), pages 55-61, April.
    7. Rachel Wheatley & Julio Diaz Caballero & Natalia Kapel & Fien H. R. Winter & Pramod Jangir & Angus Quinn & Ester Barrio-Tofiño & Carla López-Causapé & Jessica Hedge & Gabriel Torrens & Thomas Schalk &, 2021. "Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection," Nature Communications, Nature, vol. 12(1), pages 1-12, 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. Rachel M. Wheatley & Julio Diaz Caballero & Thomas E. Schalk & Fien H. R. Winter & Liam P. Shaw & Natalia Kapel & Claudia Recanatini & Leen Timbermont & Jan Kluytmans & Mark Esser & Alicia Lacoma & Cr, 2022. "Gut to lung translocation and antibiotic mediated selection shape the dynamics of Pseudomonas aeruginosa in an ICU patient," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. David B. Stern & Nathan W. Anderson & Juanita A. Diaz & Carol Eunmi Lee, 2022. "Genome-wide signatures of synergistic epistasis during parallel adaptation in a Baltic Sea copepod," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Song Li & Wenbin Yu & Fei Xie & Haitao Luo & Zhimin Liu & Weiwei Lv & Duanbo Shi & Dexin Yu & Peng Gao & Cheng Chen & Meng Wei & Wenhao Zhou & Jiaqian Wang & Zhikun Zhao & Xin Dai & Qian Xu & Xue Zhan, 2023. "Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Lichun Ma & Sophia Heinrich & Limin Wang & Friederike L. Keggenhoff & Subreen Khatib & Marshonna Forgues & Michael Kelly & Stephen M. Hewitt & Areeba Saif & Jonathan M. Hernandez & Donna Mabry & Roman, 2022. "Multiregional single-cell dissection of tumor and immune cells reveals stable lock-and-key features in liver cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Gabriela Montejo-Kovacevich & Joana I. Meier & Caroline N. Bacquet & Ian A. Warren & Yingguang Frank Chan & Marek Kucka & Camilo Salazar & Nicol Rueda-M & Stephen H. Montgomery & W. Owen McMillan & Kr, 2022. "Repeated genetic adaptation to altitude in two tropical butterflies," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Julian Petersen & Lukas Englmaier & Artem V. Artemov & Irina Poverennaya & Ruba Mahmoud & Thibault Bouderlique & Marketa Tesarova & Ruslan Deviatiiarov & Anett Szilvásy-Szabó & Evgeny E. Akkuratov & D, 2023. "A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    7. Hattie Chung & Christina Merakou & Matthew M. Schaefers & Kelly B. Flett & Sarah Martini & Roger Lu & Jennifer A. Blumenthal & Shanice S. Webster & Ashley R. Cross & Roy Al Ahmar & Erin Halpin & Miche, 2022. "Rapid expansion and extinction of antibiotic resistance mutations during treatment of acute bacterial respiratory infections," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    8. Noushin Niknafs & Violeta Beleva-Guthrie & Daniel Q Naiman & Rachel Karchin, 2015. "SubClonal Hierarchy Inference from Somatic Mutations: Automatic Reconstruction of Cancer Evolutionary Trees from Multi-region Next Generation Sequencing," PLOS Computational Biology, Public Library of Science, vol. 11(10), pages 1-26, October.
    9. Albert H Gough & Ning Chen & Tong Ying Shun & Timothy R Lezon & Robert C Boltz & Celeste E Reese & Jacob Wagner & Lawrence A Vernetti & Jennifer R Grandis & Adrian V Lee & Andrew M Stern & Mark E Schu, 2014. "Identifying and Quantifying Heterogeneity in High Content Analysis: Application of Heterogeneity Indices to Drug Discovery," PLOS ONE, Public Library of Science, vol. 9(7), pages 1-16, July.
    10. Saakian, David B. & Vardanyan, Edgar & Yakushkina, Tatiana, 2020. "Evolutionary model with recombination and randomly changing fitness landscape," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 541(C).
    11. Joseph G. Kern & Andrew M. Tilston-Lunel & Anthony Federico & Boting Ning & Amy Mueller & Grace B. Peppler & Eleni Stampouloglou & Nan Cheng & Randy L. Johnson & Marc E. Lenburg & Jennifer E. Beane & , 2022. "Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    12. Christopher R S Banerji & Simone Severini & Carlos Caldas & Andrew E Teschendorff, 2015. "Intra-Tumour Signalling Entropy Determines Clinical Outcome in Breast and Lung Cancer," PLOS Computational Biology, Public Library of Science, vol. 11(3), pages 1-23, March.
    13. Yukinari Haraoka & Yuki Akieda & Yuri Nagai & Chihiro Mogi & Tohru Ishitani, 2022. "Zebrafish imaging reveals TP53 mutation switching oncogene-induced senescence from suppressor to driver in primary tumorigenesis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. J. Carlos R. Hernandez-Beltran & Jerónimo Rodríguez-Beltrán & Oscar Bruno Aguilar-Luviano & Jesús Velez-Santiago & Octavio Mondragón-Palomino & R. Craig MacLean & Ayari Fuentes-Hernández & Alvaro San , 2024. "Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    15. Anna A Schönherz & Julie Støve Bødker & Alexander Schmitz & Rasmus Froberg Brøndum & Lasse Hjort Jakobsen & Anne Stidsholt Roug & Marianne T Severinsen & Tarec C El-Galaly & Paw Jensen & Hans Erik Joh, 2020. "Normal myeloid progenitor cell subset-associated gene signatures for acute myeloid leukaemia subtyping with prognostic impact," PLOS ONE, Public Library of Science, vol. 15(4), pages 1-21, April.
    16. Olesia Werbowy & Sławomir Werbowy & Tadeusz Kaczorowski, 2017. "Plasmid stability analysis based on a new theoretical model employing stochastic simulations," PLOS ONE, Public Library of Science, vol. 12(8), pages 1-21, August.
    17. Gal Feller & Razia Abdool Gafaar Khammissa & Raoul Ballyram & Mia-Michaela Beetge & Johan Lemmer & Liviu Feller, 2023. "Tumour Genetic Heterogeneity in Relation to Oral Squamous Cell Carcinoma and Anti-Cancer Treatment," IJERPH, MDPI, vol. 20(3), pages 1-10, January.
    18. Shravana kumar chinnikatti, 2017. "Cancer and its Genomics in Transformation Era," Cancer Therapy & Oncology International Journal, Juniper Publishers Inc., vol. 7(2), pages 25-26, September.
    19. Duy Pham & Xiao Tan & Brad Balderson & Jun Xu & Laura F. Grice & Sohye Yoon & Emily F. Willis & Minh Tran & Pui Yeng Lam & Arti Raghubar & Priyakshi Kalita-de Croft & Sunil Lakhani & Jana Vukovic & Ma, 2023. "Robust mapping of spatiotemporal trajectories and cell–cell interactions in healthy and diseased tissues," Nature Communications, Nature, vol. 14(1), pages 1-25, December.
    20. Xiaodong Liu & Ke Zhang & Neslihan A. Kaya & Zhe Jia & Dafei Wu & Tingting Chen & Zhiyuan Liu & Sinan Zhu & Axel M. Hillmer & Torsten Wuestefeld & Jin Liu & Yun Shen Chan & Zheng Hu & Liang Ma & Li Ji, 2024. "Tumor phylogeography reveals block-shaped spatial heterogeneity and the mode of evolution in Hepatocellular Carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    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:14:y:2023:i:1:d:10.1038_s41467-023-39416-2. 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.