1. Structural Biology and Molecular Biophysics
  2. Microbiology and Infectious Disease
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Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions

  1. Caitlin N Spaulding
  2. Henry Louis Schreiber
  3. Weili Zheng
  4. Karen W Dodson
  5. Jennie E Hazen
  6. Matt S Conover
  7. Fengbin Wang
  8. Pontus Svenmarker
  9. Areli Luna-Rico
  10. Olivera Francetic
  11. Magnus Andersson
  12. Scott Hultgren  Is a corresponding author
  13. Edward H Egelman
  1. Washington University School of Medicine, United States
  2. University of Virginia, United States
  3. Umeå University, Sweden
  4. Institut Pasteur, France
Research Article
  • Cited 17
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Cite this article as: eLife 2018;7:e31662 doi: 10.7554/eLife.31662

Abstract

Uropathogenic E. coli (UPEC), which cause urinary tract infections (UTI), utilize type 1 pili, a chaperone usher pathway (CUP) pilus, to cause UTI and colonize the gut. The pilus rod, comprised of repeating FimA subunits, provides a structural scaffold for displaying the tip adhesin, FimH. We solved the 4.2 Å resolution structure of the type 1 pilus rod using cryo-electron microscopy. Residues forming the interactive surfaces that determine the mechanical properties of the rod were maintained by selection based on a global alignment of fimA sequences. We identified mutations that did not alter pilus production in vitro but reduced the force required to unwind the rod. UPEC expressing these mutant pili were significantly attenuated in bladder infection and intestinal colonization in mice. This study elucidates an unappreciated functional role for the molecular spring-like property of type 1 pilus rods in host-pathogen interactions and carries important implications for other pilus-mediated diseases.

Article and author information

Author details

  1. Caitlin N Spaulding

    Center for Women's Infectious Disease Research, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.
  2. Henry Louis Schreiber

    Center for Women's Infectious Disease Research, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4501-9886
  3. Weili Zheng

    Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, United States
    Competing interests
    No competing interests declared.
  4. Karen W Dodson

    Center for Women's Infectious Disease Research, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.
  5. Jennie E Hazen

    Center for Women's Infectious Disease Research, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.
  6. Matt S Conover

    Center for Women's Infectious Disease Research, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.
  7. Fengbin Wang

    Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, United States
    Competing interests
    No competing interests declared.
  8. Pontus Svenmarker

    Department of Physics, Umeå University, Umeå, Sweden
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1308-4923
  9. Areli Luna-Rico

    Biochemistry of Macromolecular Interactions Unit, Department of Structural Biology and Chemistry, Institut Pasteur, Paris, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7538-5441
  10. Olivera Francetic

    Biochemistry of Macromolecular Interactions Unit, Department of Structural Biology and Chemistry, Institut Pasteur, Paris, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4145-5314
  11. Magnus Andersson

    Department of Physics, Umeå University, Umeå, Sweden
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9835-3263
  12. Scott Hultgren

    Center for Women's Infectious Disease Research, Washington University School of Medicine, St Louis, United States
    For correspondence
    hultgren@wustl.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8785-564X
  13. Edward H Egelman

    Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, United States
    Competing interests
    Edward H Egelman, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4844-5212

Funding

National Institutes of Health (GM122510)

  • Edward H Egelman

Washington University School of Medicine (Monsanto Excellence Fund Graduate Fellowship)

  • Henry Louis Schreiber

National Institutes of Health (AI048689)

  • Scott Hultgren

National Institutes of Health (DK064540)

  • Scott Hultgren

National Institutes of Health (1F31DK107057)

  • Caitlin N Spaulding

National Institutes of Health (DK101171-02)

  • Matt S Conover

Svenska Forskningsrådet Formas (621-2013-5379)

  • Magnus Andersson

Agence Nationale de la Recherche (ANR-14-CE09-0004)

  • Olivera Francetic

Paris Pasteur University (Graduate Research Fellowship)

  • Areli Luna-Rico

Washington University School of Medicine (Lucille P. Markey Pathway for Pathobiology)

  • Henry Louis Schreiber

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

Ethics

Animal experimentation: The Washington University Animal Studies Committee approved all procedures used for the mouse experiments described in the present study (Protocol Application Number 20150226). Overall care of the animals was consistent with The Guide for the Care and Use of Laboratory Animals from the National Research Council and the USDA Animal Care Resource Guide. Every effort was made to minimize suffering.

Reviewing Editor

  1. Michael S Gilmore, Harvard Medical School, United States

Publication history

  1. Received: August 31, 2017
  2. Accepted: January 12, 2018
  3. Accepted Manuscript published: January 18, 2018 (version 1)
  4. Version of Record published: February 5, 2018 (version 2)

Copyright

© 2018, Spaulding 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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