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© 2018, Spaulding et al. This work is licensed under the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/3.0/ ) (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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.

Details

Title
Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions
Author
Spaulding, Caitlin N; Schreiber, Henry Louis, IV; Zheng Weili; Dodson, Karen W; Hazen, Jennie E; Conover, Matt S; Wang Fengbin; Svenmarker Pontus; Luna-Rico Areli; Olivera, Francetic; Andersson, Magnus; Hultgren, Scott; Egelman, Edward H
University/institution
U.S. National Institutes of Health/National Library of Medicine
Publication year
2018
Publication date
2018
Publisher
eLife Sciences Publications Ltd.
e-ISSN
2050084X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2009160143
Copyright
© 2018, Spaulding et al. This work is licensed under the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/3.0/ ) (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.