IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39553-8.html
   My bibliography  Save this article

Regulation of the macrolide resistance ABC-F translation factor MsrD

Author

Listed:
  • Corentin R. Fostier

    (Université Paris Cité, Institut de Biologie Physico-Chimique)

  • Farès Ousalem

    (Université Paris Cité, Institut de Biologie Physico-Chimique)

  • Elodie C. Leroy

    (Univ. Bordeaux, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale)

  • Saravuth Ngo

    (Université Paris Cité, Institut de Biologie Physico-Chimique)

  • Heddy Soufari

    (Univ. Bordeaux, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale
    SPT Labtech Ltd.)

  • C. Axel Innis

    (Univ. Bordeaux, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale)

  • Yaser Hashem

    (Univ. Bordeaux, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale)

  • Grégory Boël

    (Université Paris Cité, Institut de Biologie Physico-Chimique)

Abstract

Antibiotic resistance ABC-Fs (ARE ABC-Fs) are translation factors that provide resistance against clinically important ribosome-targeting antibiotics which are proliferating among pathogens. Here, we combine genetic and structural approaches to determine the regulation of streptococcal ARE ABC-F gene msrD in response to macrolide exposure. We show that binding of cladinose-containing macrolides to the ribosome prompts insertion of the leader peptide MsrDL into a crevice of the ribosomal exit tunnel, which is conserved throughout bacteria and eukaryotes. This leads to a local rearrangement of the 23 S rRNA that prevents peptide bond formation and accommodation of release factors. The stalled ribosome obstructs the formation of a Rho-independent terminator structure that prevents msrD transcriptional attenuation. Erythromycin induction of msrD expression via MsrDL, is suppressed by ectopic expression of mrsD, but not by mutants which do not provide antibiotic resistance, showing correlation between MsrD function in antibiotic resistance and its action on this stalled complex.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39553-8
    DOI: 10.1038/s41467-023-39553-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39553-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39553-8?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. Stefan Arenz & Haripriya Ramu & Pulkit Gupta & Otto Berninghausen & Roland Beckmann & Nora Vázquez-Laslop & Alexander S. Mankin & Daniel N. Wilson, 2014. "Molecular basis for erythromycin-dependent ribosome stalling during translation of the ErmBL leader peptide," Nature Communications, Nature, vol. 5(1), pages 1-8, May.
    2. Caillan Crowe-McAuliffe & Victoriia Murina & Kathryn Jane Turnbull & Susanne Huch & Marje Kasari & Hiraku Takada & Lilit Nersisyan & Arnfinn Sundsfjord & Kristin Hegstad & Gemma C. Atkinson & Vicent P, 2022. "Structural basis for PoxtA-mediated resistance to phenicol and oxazolidinone antibiotics," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. 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.
    4. Caillan Crowe-McAuliffe & Victoriia Murina & Kathryn Jane Turnbull & Marje Kasari & Merianne Mohamad & Christine Polte & Hiraku Takada & Karolis Vaitkevicius & Jörgen Johansson & Zoya Ignatova & Gemma, 2021. "Structural basis of ABCF-mediated resistance to pleuromutilin, lincosamide, and streptogramin A antibiotics in Gram-positive pathogens," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    5. Anne-Xander Stel & Emily R. Gordon & Arnab Sengupta & Allyson K. Martínez & Dorota Klepacki & Thomas N. Perry & Alba Herrero del Valle & Nora Vázquez-Laslop & Matthew S. Sachs & Luis R. Cruz-Vera & C., 2021. "Structural basis for the tryptophan sensitivity of TnaC-mediated ribosome stalling," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    6. Stefan Arenz & Lars V. Bock & Michael Graf & C. Axel Innis & Roland Beckmann & Helmut Grubmüller & Andrea C. Vaiana & Daniel N. Wilson, 2016. "A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest," Nature Communications, Nature, vol. 7(1), pages 1-14, November.
    7. T. Martin Schmeing & Kevin S. Huang & Scott A. Strobel & Thomas A. Steitz, 2005. "An induced-fit mechanism to promote peptide bond formation and exclude hydrolysis of peptidyl-tRNA," Nature, Nature, vol. 438(7067), pages 520-524, November.
    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. Martino Morici & Sara Gabrielli & Keigo Fujiwara & Helge Paternoga & Bertrand Beckert & Lars V. Bock & Shinobu Chiba & Daniel N. Wilson, 2024. "RAPP-containing arrest peptides induce translational stalling by short circuiting the ribosomal peptidyltransferase activity," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Sakshi Jain & Lukasz Koziej & Panagiotis Poulis & Igor Kaczmarczyk & Monika Gaik & Michal Rawski & Namit Ranjan & Sebastian Glatt & Marina V. Rodnina, 2023. "Modulation of translational decoding by m6A modification of mRNA," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Felix Gersteuer & Martino Morici & Sara Gabrielli & Keigo Fujiwara & Haaris A. Safdari & Helge Paternoga & Lars V. Bock & Shinobu Chiba & Daniel N. Wilson, 2024. "The SecM arrest peptide traps a pre-peptide bond formation state of the ribosome," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Thu Giang Nguyen & Christina Ritter & Eva Kummer, 2023. "Structural insights into the role of GTPBP10 in the RNA maturation of the mitoribosome," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. 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.
    6. Victor E. Cruz & Christine S. Weirich & Nagesh Peddada & Jan P. Erzberger, 2024. "The DEAD-box ATPase Dbp10/DDX54 initiates peptidyl transferase center formation during 60S ribosome biogenesis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Caillan Crowe-McAuliffe & Victoriia Murina & Kathryn Jane Turnbull & Susanne Huch & Marje Kasari & Hiraku Takada & Lilit Nersisyan & Arnfinn Sundsfjord & Kristin Hegstad & Gemma C. Atkinson & Vicent P, 2022. "Structural basis for PoxtA-mediated resistance to phenicol and oxazolidinone antibiotics," Nature Communications, Nature, vol. 13(1), pages 1-13, 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_s41467-023-39553-8. 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.