IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31057-1.html
   My bibliography  Save this article

Extracellular release of two peptidases dominates generation of the trypanosome quorum-sensing signal

Author

Listed:
  • Mabel Deladem Tettey

    (Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh)

  • Federico Rojas

    (Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh
    Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University)

  • Keith R. Matthews

    (Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh)

Abstract

Trypanosomes causing African sleeping sickness use quorum-sensing (QS) to generate transmission-competent stumpy forms in mammalian hosts. This density-dependent process is signalled by oligopeptides that stimulate the signal transduction pathway leading to stumpy formation. Here, using mass spectrometry analysis, we identify peptidases released by trypanosomes and, for 12 peptidases, confirm their extracellular delivery. Thereafter, we determine the contribution of each peptidase to QS signal production using systematic inducible overexpression in vivo, and confirm this activity operates through the physiological QS signalling pathway. Gene knockout of the QS-active peptidases identifies two enzymes, oligopeptidase B and metallocarboxypeptidase 1, that significantly reduce QS when ablated individually. Further, combinatorial gene knockout of both peptidases confirms their dominance in the generation of the QS signal, with peptidase release of oligopeptidase B mediated via an unconventional protein secretion pathway. This work identifies how the QS signal driving trypanosome virulence and transmission is generated in mammalian hosts.

Suggested Citation

  • Mabel Deladem Tettey & Federico Rojas & Keith R. Matthews, 2022. "Extracellular release of two peptidases dominates generation of the trypanosome quorum-sensing signal," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31057-1
    DOI: 10.1038/s41467-022-31057-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31057-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-31057-1?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. Samuel Dean & Rosa Marchetti & Kiaran Kirk & Keith R. Matthews, 2009. "A surface transporter family conveys the trypanosome differentiation signal," Nature, Nature, vol. 459(7244), pages 213-217, May.
    2. Emma M. Briggs & Federico Rojas & Richard McCulloch & Keith R. Matthews & Thomas D. Otto, 2021. "Single-cell transcriptomic analysis of bloodstream Trypanosoma brucei reconstructs cell cycle progression and developmental quorum sensing," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    3. Binny M. Mony & Paula MacGregor & Alasdair Ivens & Federico Rojas & Andrew Cowton & Julie Young & David Horn & Keith Matthews, 2014. "Genome-wide dissection of the quorum sensing signalling pathway in Trypanosoma brucei," Nature, Nature, vol. 505(7485), pages 681-685, January.
    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. Juan F. Quintana & Praveena Chandrasegaran & Matthew C. Sinton & Emma M. Briggs & Thomas D. Otto & Rhiannon Heslop & Calum Bentley-Abbot & Colin Loney & Luis de Lecea & Neil A. Mabbott & Annette MacLe, 2022. "Single cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Mathieu Cayla & Christos Spanos & Kirsty McWilliam & Eliza Waskett & Juri Rappsilber & Keith R. Matthews, 2024. "Differentiation granules, a dynamic regulator of T. brucei development," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Anna Trenaman & Michele Tinti & Richard J. Wall & David Horn, 2024. "Post-transcriptional reprogramming by thousands of mRNA untranslated regions in trypanosomes," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Christian Reuter & Laura Hauf & Fabian Imdahl & Rituparno Sen & Ehsan Vafadarnejad & Philipp Fey & Tamara Finger & Nicola G. Jones & Heike Walles & Lars Barquist & Antoine-Emmanuel Saliba & Florian Gr, 2023. "Vector-borne Trypanosoma brucei parasites develop in artificial human skin and persist as skin tissue forms," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Joana R. C. Faria & Michele Tinti & Catarina A. Marques & Martin Zoltner & Harunori Yoshikawa & Mark C. Field & David Horn, 2023. "An allele-selective inter-chromosomal protein bridge supports monogenic antigen expression in the African trypanosome," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Hien Thi Thu Pham & Stefan Magez & Boyoon Choi & Bolortsetseg Baatar & Joohee Jung & Magdalena Radwanska, 2023. "Neutrophil metalloproteinase driven spleen damage hampers infection control of trypanosomiasis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. Eva Horáková & Laurence Lecordier & Paula Cunha & Roman Sobotka & Piya Changmai & Catharina J. M. Langedijk & Jan Van Den Abbeele & Benoit Vanhollebeke & Julius Lukeš, 2022. "Heme-deficient metabolism and impaired cellular differentiation as an evolutionary trade-off for human infectivity in Trypanosoma brucei gambiense," Nature Communications, Nature, vol. 13(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:13:y:2022:i:1:d:10.1038_s41467-022-31057-1. 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.