Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions
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...
| Main Authors: | , , , , , , , , , , , , |
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| Formato: | Artigo |
| Idioma: | English |
| Publicado em: |
eLife Sciences Publications Ltd
2018-01-01
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| Colecção: | eLife |
| Assuntos: | |
| Acesso em linha: | https://elifesciences.org/articles/31662 |
| _version_ | 1828169112889589760 |
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| author | Caitlin N Spaulding Henry Louis Schreiber IV Weili Zheng Karen W Dodson Jennie E Hazen Matt S Conover Fengbin Wang Pontus Svenmarker Areli Luna-Rico Olivera Francetic Magnus Andersson Scott Hultgren Edward H Egelman |
| author_facet | Caitlin N Spaulding Henry Louis Schreiber IV Weili Zheng Karen W Dodson Jennie E Hazen Matt S Conover Fengbin Wang Pontus Svenmarker Areli Luna-Rico Olivera Francetic Magnus Andersson Scott Hultgren Edward H Egelman |
| author_sort | Caitlin N Spaulding |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:45:51Z |
| format | Article |
| id | doaj.art-f1a3fc529d8f44c8bf4d356b718bbe0c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:45:51Z |
| publishDate | 2018-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f1a3fc529d8f44c8bf4d356b718bbe0c2022-12-22T03:51:10ZengeLife Sciences Publications LtdeLife2050-084X2018-01-01710.7554/eLife.31662Functional role of the type 1 pilus rod structure in mediating host-pathogen interactionsCaitlin N Spaulding0https://orcid.org/0000-0002-7582-3816Henry Louis Schreiber IV1https://orcid.org/0000-0002-4501-9886Weili Zheng2Karen W Dodson3Jennie E Hazen4Matt S Conover5Fengbin Wang6Pontus Svenmarker7https://orcid.org/0000-0002-1308-4923Areli Luna-Rico8https://orcid.org/0000-0001-7538-5441Olivera Francetic9https://orcid.org/0000-0002-4145-5314Magnus Andersson10https://orcid.org/0000-0002-9835-3263Scott Hultgren11https://orcid.org/0000-0001-8785-564XEdward H Egelman12https://orcid.org/0000-0003-4844-5212Center for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, United States; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, United StatesCenter for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, United States; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, United StatesDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, United StatesCenter for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, United States; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, United StatesCenter for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, United States; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, United StatesCenter for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, United States; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, United StatesDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, United StatesDepartment of Physics, Umeå University, Umeå, SwedenDepartment of Structural Biology and Chemistry, Institut Pasteur, Biochemistry of Macromolecular Interactions Unit, Paris, FranceDepartment of Structural Biology and Chemistry, Institut Pasteur, Biochemistry of Macromolecular Interactions Unit, Paris, FranceDepartment of Physics, Umeå University, Umeå, SwedenCenter for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, United States; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, United StatesDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, United StatesUropathogenic 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.https://elifesciences.org/articles/31662Chaperone-usher pathway piliCUP pilitype 1 pilicryo-EMUPECUTI |
| spellingShingle | Caitlin N Spaulding Henry Louis Schreiber IV Weili Zheng Karen W Dodson Jennie E Hazen Matt S Conover Fengbin Wang Pontus Svenmarker Areli Luna-Rico Olivera Francetic Magnus Andersson Scott Hultgren Edward H Egelman Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions eLife Chaperone-usher pathway pili CUP pili type 1 pili cryo-EM UPEC UTI |
| title | Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions |
| title_full | Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions |
| title_fullStr | Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions |
| title_full_unstemmed | Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions |
| title_short | Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions |
| title_sort | functional role of the type 1 pilus rod structure in mediating host pathogen interactions |
| topic | Chaperone-usher pathway pili CUP pili type 1 pili cryo-EM UPEC UTI |
| url | https://elifesciences.org/articles/31662 |
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