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Elife. 2018 Jan 18;7. pii: e31662. doi: 10.7554/eLife.31662.

Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions.

Author information

1
Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, United States.
2
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, United States.
3
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, United States.
4
Department of Physics, Umeå University, Umeå, Sweden.
5
Department of Structural Biology and Chemistry, Institut Pasteur, Biochemistry of Macromolecular Interactions Unit, Paris, France.
#
Contributed equally

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.

KEYWORDS:

CUP pili; Chaperone-usher pathway pili; E. coli; UPEC; UTI; biophysics; cryo-EM; infectious disease; microbiology; mouse; structural biology; type 1 pili

PMID:
29345620
PMCID:
PMC5798934
DOI:
10.7554/eLife.31662
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

CS, HS, WZ, KD, JH, MC, FW, PS, AL, OF, MA, SH No competing interests declared, EE Reviewing editor, <italic>eLife</italic>

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