title: Binding of CFA/I Pili of Enterotoxigenic Escherichia coli to Asialo-GM1 Is Mediated by the Minor Pilin CfaE.
abstract: CFA/I pili are representatives of a large family of related pili that mediate the adherence of enterotoxigenic Escherichia coli to intestinal epithelial cells. They are assembled via the alternate chaperone-usher pathway and consist of two subunits, CfaB, which makes up the pilus shaft and a single pilus tip-associated subunit, CfaE. The current model of pilus-mediated adherence proposes that CFA/I has two distinct binding activities; the CfaE subunit is responsible for binding to receptors of unknown structure on erythrocyte and intestinal epithelial cell surfaces, while CfaB binds to various glycosphingolipids, including asialo-GM1. In this report, we present two independent lines of evidence that, contrary to the existing model, CfaB does not bind to asialo-GM1 independently of CfaE. Neither purified CfaB subunits nor CfaB assembled into pili bind to asialo-GM1. Instead, we demonstrate that binding activity toward asialo-GM1 resides in CfaE and this is essential for pilus binding to Caco-2 intestinal epithelial cells. We conclude that the binding activities of CFA/I pili for asialo-GM1, erythrocytes, and intestinal cells are inseparable, require the same amino acid residues in CfaE, and therefore depend on the same or very similar binding mechanisms.
authors.affiliation: Menzies Health Institute Queensland, School of Medical Sciences, Griffith University, Southport, QLD, Australia.
authors.forename: T P Vipin
authors.initials: TPV
authors.lastname: Madhavan
authors.affiliation: Institute for Future Environments and School of Earth, Environmental and Biological Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
authors.forename: James D
authors.initials: JD
authors.lastname: Riches
authors.affiliation: Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Scanlon
authors.affiliation: Menzies Health Institute Queensland, School of Medical Sciences, Griffith University, Southport, QLD, Australia.
authors.forename: Glen C
authors.identifier: http://orcid.org/0000-0002-9638-8091
authors.initials: GC
authors.lastname: Ulett
authors.affiliation: Menzies Health Institute Queensland, School of Medical Sciences, Griffith University, Southport, QLD, Australia h.sakellaris@griffith.edu.au.|School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, WA, Australia.
authors.forename: Harry
authors.initials: H
authors.lastname: Sakellaris
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D018938:Caco-2 Cells; D054307:Enterotoxigenic Escherichia coli / Q000502:physiology*; D004847:Epithelial Cells / Q000382:microbiology; D004912:Erythrocytes / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000378:metabolism*; D036781:Fimbriae Proteins / Q000378:metabolism*; D010861:Fimbriae, Bacterial / Q000502:physiology*; D005677:G(M1) Ganglioside / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D011817:Rabbits
chemical_list: C559939:CfaE protein, E coli; D029968:Escherichia coli Proteins; D036781:Fimbriae Proteins; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside