title: Antibody-mediated disruption of the mechanics of CS20 fimbriae of enterotoxigenic Escherichia coli.
abstract: Preventive vaccines against enterotoxigenic Escherichia coli (ETEC) are being developed, many of which target common fimbrial colonization factors as the major constituent, based on empirical evidence that these function as protective antigens. Particularly, passive oral administration of ETEC anti-fimbrial antibodies prevent ETEC diarrhea. Little is, however, known regarding the specific mechanisms by which intestinal antibodies against ETEC fimbriae function to prevent disease. Using coli surface antigen 20 (CS20) fimbriae as a model ETEC colonization factor, we show using force spectroscopy that anti-fimbrial antibodies diminish fimbrial elasticity by inhibiting their natural capacity to unwind and rewind. In the presence of anti-CS20 antibodies the force required to unwind a single fimbria was increased several-fold and the extension length was shortened several-fold. Similar measurements in the presence of anti-CS20 Fab fragments did not show any effect, indicating that bivalent antibody binding is required to reduce fimbrial elasticity. Based on these findings, we propose a model for an in-vivo mechanism whereby antibody-mediated disruption of the biomechanical properties of CS20 fimbriae impedes sustained adhesion of ETEC to the intestinal mucosal surface. Further elucidation of the role played by intestinal antibodies in mechanical disruption of fimbrial function may provide insights relevant to ETEC vaccine development.
authors.affiliation: Department of Physics, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Bhupender
authors.initials: B
authors.lastname: Singh
authors.affiliation: Department of Physics, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Narges
authors.initials: N
authors.lastname: Mortezaei
authors.affiliation: The Laboratory for Molecular Infection Medicine Sweden (MIMS) and Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Bernt Eric
authors.initials: BE
authors.lastname: Uhlin
authors.affiliation: Enteric Diseases Department, Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, MD 20910, USA.|Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Savarino
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Esther
authors.initials: E
authors.lastname: Bullitt
authors.affiliation: Department of Physics, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Andersson
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D054307:Enterotoxigenic Escherichia coli / Q000276:immunology* / Q000378:metabolism*; D036781:Fimbriae Proteins / Q000276:immunology; D010861:Fimbriae, Bacterial / Q000276:immunology*; D008954:Models, Biological; D009010:Monte Carlo Method; D011485:Protein Binding / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D036781:Fimbriae Proteins