Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions
- Washington University School of Medicine, United States
- University of Virginia, United States
- Umeå University, Sweden
- Institut Pasteur, France
- Cited 3
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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
Henry Louis Schreiber
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
- Michael S Gilmore, Harvard Medical School, United States
Publication history
- Received: August 31, 2017
- Accepted: January 12, 2018
- Accepted Manuscript published: January 18, 2018 (version 1)
- 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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