IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-15282-0.html
   My bibliography  Save this article

Lipid analogs reveal features critical for hemolysis and diminish granadaene mediated Group B Streptococcus infection

Author

Listed:
  • Blair Armistead

    (University of Washington
    Seattle Children’s Research Institute)

  • Pilar Herrero-Foncubierta

    (University of Granada)

  • Michelle Coleman

    (Seattle Children’s Research Institute)

  • Phoenicia Quach

    (Seattle Children’s Research Institute)

  • Christopher Whidbey

    (University of Washington
    Seattle Children’s Research Institute
    Seattle University)

  • Jose Justicia

    (University of Granada)

  • Ruben Tapia

    (University of Granada)

  • Raquel Casares

    (University of Granada)

  • Alba Millán

    (University of Granada)

  • Ali Haidour

    (University of Granada)

  • Javier Rodriguez Granger

    (Virgen de las Nieves Hospital)

  • Jay Vornhagen

    (University of Washington
    Seattle Children’s Research Institute
    University of Michigan)

  • Verónica Santana-Ufret

    (Seattle Children’s Research Institute)

  • Sean Merillat

    (Seattle Children’s Research Institute)

  • Kristina Adams Waldorf

    (University of Washington
    University of Washington School of Medicine
    University of Washington
    University of Gothenburg)

  • Juan Manuel Cuerva

    (University of Granada)

  • Lakshmi Rajagopal

    (University of Washington
    Seattle Children’s Research Institute
    University of Washington School of Medicine)

Abstract

Although certain microbial lipids are toxins, the structural features important for cytotoxicity remain unknown. Increased functional understanding is essential for developing therapeutics against toxic microbial lipids. Group B Streptococci (GBS) are bacteria associated with preterm births, stillbirths, and severe infections in neonates and adults. GBS produce a pigmented, cytotoxic lipid, known as granadaene. Despite its importance to all manifestations of GBS disease, studies towards understanding granadaene’s toxic activity are hindered by its instability and insolubility in purified form. Here, we report the synthesis and screening of lipid derivatives inspired by granadaene, which reveal features central to toxin function, namely the polyene chain length. Furthermore, we show that vaccination with a non-toxic synthetic analog confers the production of antibodies that inhibit granadaene-mediated hemolysis ex vivo and diminish GBS infection in vivo. This work provides unique structural and functional insight into granadaene and a strategy to mitigate GBS infection, which will be relevant to other toxic lipids encoded by human pathogens.

Suggested Citation

  • Blair Armistead & Pilar Herrero-Foncubierta & Michelle Coleman & Phoenicia Quach & Christopher Whidbey & Jose Justicia & Ruben Tapia & Raquel Casares & Alba Millán & Ali Haidour & Javier Rodriguez Gra, 2020. "Lipid analogs reveal features critical for hemolysis and diminish granadaene mediated Group B Streptococcus infection," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15282-0
    DOI: 10.1038/s41467-020-15282-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-15282-0
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-020-15282-0?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Cosme Claverie & Francesco Coppolino & Maria-Vittoria Mazzuoli & Cécile Guyonnet & Elise Jacquemet & Rachel Legendre & Odile Sismeiro & Giuseppe Valerio Gaetano & Giuseppe Teti & Patrick Trieu-Cuot & , 2024. "Constitutive activation of two-component systems reveals regulatory network interactions in Streptococcus agalactiae," Nature Communications, Nature, vol. 15(1), pages 1-12, 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:11:y:2020:i:1:d:10.1038_s41467-020-15282-0. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.