Typhoid toxin sorting and exocytic transport from Salmonella Typhi infected cells

  1. Shu-Jung Chang
  2. Yu-Ting Hsu
  3. Yun Chen
  4. Yen-Yi Lin
  5. Maria Lara-Tejero
  6. Jorge E Galan  Is a corresponding author
  1. Yale University School of Medicine, United States
  2. National Taiwan University, Taiwan

Abstract

Typhoid toxin is an essential virulence factor for Salmonella Typhi, the cause of typhoid fever in humans. This toxin has an unusual biology in that it is produced by Salmonella Typhi only when located within host cells. Once synthesized, the toxin is secreted to the lumen of the Salmonella-containing vacuole from where it is transported to the extracellular space by vesicle carrier intermediates. Here we report the identification of the typhoid toxin sorting receptor and components of the cellular machinery that packages the toxin into vesicle carriers, and exports it to the extracellular space. We found that the cation-independent mannose-6-phosphate receptor serves as typhoid toxin sorting receptor and that the coat protein COPII and the GTPase Sar1 mediate its packaging into vesicle carriers. Formation of the typhoid toxin carriers requires the specific environment of the Salmonella Typhi-containing vacuole, which is determined by the activities of specific effectors of its type III protein secretion systems. We also found that Rab11B and its interacting protein Rip11 control the intracellular transport of the typhoid toxin carriers, and the SNARE proteins VAMP7, SNAP23, and Syntaxin 4 their fusion to the plasma membrane. Typhoid toxin's cooption of specific cellular machinery for its transport to the extracellular space illustrates the remarkable adaptation of an exotoxin to exert its function in the context of an intracellular pathogen.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files; source data files for all figures have been provided

Article and author information

Author details

  1. Shu-Jung Chang

    1Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Yu-Ting Hsu

    Graduate Institute of Microbiology, National Taiwan University, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  3. Yun Chen

    Graduate Institute of Microbiology, National Taiwan University, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  4. Yen-Yi Lin

    Graduate Institute of Microbiology, National Taiwan University, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  5. Maria Lara-Tejero

    Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1339-0859
  6. Jorge E Galan

    Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, United States
    For correspondence
    jorge.galan@yale.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6531-0355

Funding

National Institute of Allergy and Infectious Diseases (AI079022)

  • Jorge E Galan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Dominique Soldati-Favre, University of Geneva, Switzerland

Publication history

  1. Preprint posted: August 10, 2021 (view preprint)
  2. Received: March 11, 2022
  3. Accepted: May 15, 2022
  4. Accepted Manuscript published: May 17, 2022 (version 1)
  5. Version of Record published: May 27, 2022 (version 2)

Copyright

© 2022, Chang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Shu-Jung Chang
  2. Yu-Ting Hsu
  3. Yun Chen
  4. Yen-Yi Lin
  5. Maria Lara-Tejero
  6. Jorge E Galan
(2022)
Typhoid toxin sorting and exocytic transport from Salmonella Typhi infected cells
eLife 11:e78561.
https://doi.org/10.7554/eLife.78561

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