title: Structure and function of enterotoxigenic Escherichia coli fimbriae from differing assembly pathways.
abstract: Pathogenic enterotoxigenic Escherichia coli (ETEC) are the major bacterial cause of diarrhea in young children in developing countries and in travelers, causing significant mortality in children. Adhesive fimbriae are a prime virulence factor for ETEC, initiating colonization of the small intestinal epithelium. Similar to other Gram-negative bacteria, ETEC express one or more diverse fimbriae, some assembled by the chaperone-usher pathway and others by the alternate chaperone pathway. Here, we elucidate structural and biophysical aspects and adaptations of each fimbrial type to its respective host niche. CS20 fimbriae are compared with colonization factor antigen I (CFA/I) fimbriae, which are two ETEC fimbriae assembled via different pathways, and with P-fimbriae from uropathogenic E. coli. Many fimbriae unwind from their native helical filament to an extended linear conformation under force, thereby sustaining adhesion by reducing load at the point of contact between the bacterium and the target cell. CFA/I fimbriae require the least force to unwind, followed by CS20 fimbriae and then P-fimbriae, which require the highest unwinding force. We conclude from our electron microscopy reconstructions, modeling and force spectroscopy data that the target niche plays a central role in the biophysical properties of fimbriae that are critical for bacterial pathophysiology.
authors.affiliation: Department of Physics, Umeå University, SE-901 87, Umeå, Sweden.
authors.forename: Narges
authors.initials: N
authors.lastname: Mortezaei
authors.forename: Chelsea R
authors.initials: CR
authors.lastname: Epler
authors.forename: Paul P
authors.initials: PP
authors.lastname: Shao
authors.forename: Mariam
authors.initials: M
authors.lastname: Shirdel
authors.forename: Bhupender
authors.initials: B
authors.lastname: Singh
authors.forename: Annette
authors.initials: A
authors.lastname: McVeigh
authors.forename: Bernt Eric
authors.initials: BE
authors.lastname: Uhlin
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Savarino
authors.forename: Magnus
authors.initials: M
authors.lastname: Andersson
authors.forename: Esther
authors.initials: E
authors.lastname: Bullitt
mesh_terms: D054307:Enterotoxigenic Escherichia coli / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D036781:Fimbriae Proteins / Q000737:chemistry* / Q000235:genetics*; D010861:Fimbriae, Bacterial / Q000737:chemistry* / Q000378:metabolism; D008854:Microscopy, Electron; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D040681:Structural Homology, Protein
chemical_list: C022924:colonization factor antigens; D036781:Fimbriae Proteins