IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-53329-8.html
   My bibliography  Save this article

Macrolide resistance through uL4 and uL22 ribosomal mutations in Pseudomonas aeruginosa

Author

Listed:
  • Lise Goltermann

    (Department of Clinical Microbiology 9301)

  • Pablo Laborda

    (Department of Clinical Microbiology 9301)

  • Oihane Irazoqui

    (Technical University of Denmark)

  • Ivan Pogrebnyakov

    (Technical University of Denmark)

  • Maria Pals Bendixen

    (Department of Clinical Microbiology 9301)

  • Søren Molin

    (Technical University of Denmark)

  • Helle Krogh Johansen

    (Department of Clinical Microbiology 9301
    University of Copenhagen)

  • Ruggero La Rosa

    (Department of Clinical Microbiology 9301
    Technical University of Denmark)

Abstract

Macrolides are widely used antibiotics for the treatment of bacterial airway infections. Due to its elevated minimum inhibitory concentration in standardized culture media, Pseudomonas aeruginosa is considered intrinsically resistant and, therefore, antibiotic susceptibility testing against macrolides is not performed. Nevertheless, due to macrolides’ immunomodulatory effect and suppression of virulence factors, they are used for the treatment of persistent P. aeruginosa infections. Here, we demonstrate that macrolides are, instead, effective antibiotics against P. aeruginosa airway infections in an Air-Liquid Interface (ALI) infection model system resembling the human airways. Importantly, macrolide treatment in both people with cystic fibrosis and primary ciliary dyskinesia patients leads to the accumulation of uL4 and uL22 ribosomal protein mutations in P. aeruginosa which causes antibiotic resistance. Consequently, higher concentrations of antibiotics are needed to modulate the macrolide-dependent suppression of virulence. Surprisingly, even in the absence of antibiotics, these mutations also lead to a collateral reduction in growth rate, virulence and pathogenicity in airway ALI infections which are pivotal for the establishment of a persistent infection. Altogether, these results lend further support to the consideration of macrolides as de facto antibiotics against P. aeruginosa and the need for resistance monitoring upon prolonged macrolide treatment.

Suggested Citation

  • Lise Goltermann & Pablo Laborda & Oihane Irazoqui & Ivan Pogrebnyakov & Maria Pals Bendixen & Søren Molin & Helle Krogh Johansen & Ruggero La Rosa, 2024. "Macrolide resistance through uL4 and uL22 ribosomal mutations in Pseudomonas aeruginosa," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53329-8
    DOI: 10.1038/s41467-024-53329-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-53329-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-53329-8?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. Jennifer A. Bartell & Lea M. Sommer & Janus A. J. Haagensen & Anne Loch & Rocio Espinosa & Søren Molin & Helle Krogh Johansen, 2019. "Evolutionary highways to persistent bacterial infection," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    2. Ruggero La Rosa & Elio Rossi & Adam M. Feist & Helle Krogh Johansen & Søren Molin, 2021. "Compensatory evolution of Pseudomonas aeruginosa’s slow growth phenotype suggests mechanisms of adaptation in cystic fibrosis," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    3. C. K. Stover & X. Q. Pham & A. L. Erwin & S. D. Mizoguchi & P. Warrener & M. J. Hickey & F.S. L. Brinkman & W. O. Hufnagle & D. J. Kowalik & M. Lagrou & R. L. Garber & L. Goltry & E. Tolentino & S. We, 2000. "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen," Nature, Nature, vol. 406(6799), pages 959-964, August.
    4. Bertrand Beckert & Elodie C. Leroy & Shanmugapriya Sothiselvam & Lars V. Bock & Maxim S. Svetlov & Michael Graf & Stefan Arenz & Maha Abdelshahid & Britta Seip & Helmut Grubmüller & Alexander S. Manki, 2021. "Structural and mechanistic basis for translation inhibition by macrolide and ketolide antibiotics," Nature Communications, Nature, vol. 12(1), pages 1-15, 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. Manlu Zhu & Yiheng Wang & Haoyan Mu & Fei Han & Qian Wang & Yongfu Pei & Xin Wang & Xiongfeng Dai, 2024. "Plasmid-encoded phosphatase RapP enhances cell growth in non-domesticated Bacillus subtilis strains," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Farès Ousalem & Saravuth Ngo & Thomas Oïffer & Amin Omairi-Nasser & Marion Hamon & Laura Monlezun & Grégory Boël, 2024. "Global regulation via modulation of ribosome pausing by the ABC-F protein EttA," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Kimberley R. Miner & Paul Andrew Mayewski & Mary Hubbard & Kenny Broad & Heather Clifford & Imogen Napper & Ananta Gajurel & Corey Jaskolski & Wei Li & Mariusz Potocki & John Priscu, 2021. "A Perspective of the Cumulative Risks from Climate Change on Mt. Everest: Findings from the 2019 Expedition," IJERPH, MDPI, vol. 18(4), pages 1-13, February.
    4. Corentin R. Fostier & Farès Ousalem & Elodie C. Leroy & Saravuth Ngo & Heddy Soufari & C. Axel Innis & Yaser Hashem & Grégory Boël, 2023. "Regulation of the macrolide resistance ABC-F translation factor MsrD," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Andreea A. Gheorghita & Yancheng E. Li & Elena N. Kitova & Duong T. Bui & Roland Pfoh & Kristin E. Low & Gregory B. Whitfield & Marthe T. C. Walvoort & Qingju Zhang & Jeroen D. C. Codée & John S. Klas, 2022. "Structure of the AlgKX modification and secretion complex required for alginate production and biofilm attachment in Pseudomonas aeruginosa," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Hanne Hendrix & Annabel Itterbeek & Hannelore Longin & Lize Delanghe & Eveline Vriens & Marta Vallino & Eveline-Marie Lammens & Farhana Haque & Ahmed Yusuf & Jean-Paul Noben & Maarten Boon & Matthias , 2024. "PlzR regulates type IV pili assembly in Pseudomonas aeruginosa via PilZ binding," Nature Communications, Nature, vol. 15(1), pages 1-12, 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. Fenglin Li & Chun-Feng David Hou & Ravi K. Lokareddy & Ruoyu Yang & Francesca Forti & Federica Briani & Gino Cingolani, 2023. "High-resolution cryo-EM structure of the Pseudomonas bacteriophage E217," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. Shanshan Li & Keke Qian & Shan Wang & Kaiqiang Liang & Wei Yan, 2017. "Polypyrrole-Grafted Coconut Shell Biological Carbon as a Potential Adsorbent for Methyl Tert -Butyl Ether Removal: Characterization and Adsorption Capability," IJERPH, MDPI, vol. 14(2), pages 1-15, January.
    10. Manlu Zhu & Xiongfeng Dai, 2024. "Shaping of microbial phenotypes by trade-offs," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    11. Julian Trouillon & Kook Han & Ina Attrée & Stephen Lory, 2022. "The core and accessory Hfq interactomes across Pseudomonas aeruginosa lineages," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    12. Dan Xiao & Wen Zhang & Xiaoting Guo & Yidong Liu & Chunxia Hu & Shiting Guo & Zhaoqi Kang & Xianzhi Xu & Cuiqing Ma & Chao Gao & Ping Xu, 2021. "A d-2-hydroxyglutarate biosensor based on specific transcriptional regulator DhdR," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    13. Casey N. Grun & Ruchi Jain & Maren Schniederberend & Charles B. Shoemaker & Bryce Nelson & Barbara I. Kazmierczak, 2024. "Bacterial cell surface characterization by phage display coupled to high-throughput sequencing," Nature Communications, Nature, vol. 15(1), pages 1-19, 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:15:y:2024:i:1:d:10.1038_s41467-024-53329-8. 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.