title: A subfamily of Dr adhesins of Escherichia coli bind independently to decay-accelerating factor and the N-domain of carcinoembryonic antigen.
abstract: Escherichia coli expressing the Dr family of adhesins adheres to epithelial cells by binding to decay-accelerating factor (DAF) and carcinoembryonic antigen (CEA)-related cell surface proteins. The attachment of bacteria expressing Dr adhesins to DAF induces clustering of DAF around bacterial cells and also recruitment of CEA-related cell adhesion molecules. CEA, CEACAM1, and CEACAM6 have been shown to serve as receptors for some Dr adhesins (AfaE-I, AfaE-III, DraE, and DaaE). We demonstrate that AfaE-I, AfaE-V, DraE, and DaaE adhesins bind to the N-domain of CEA. To identify the residues involved in the N-CEA/DraE interaction, we performed SPR binding analyses of naturally occurring variants and a number of randomly generated mutants in DraE and N-CEA. Additionally, we used chemical shift mapping by NMR to determine the surface of DraE involved in N-CEA binding. These results show a distinct CEA binding site located primarily in the A, B, E, and D strands of the Dr adhesin. Interestingly, this site is located opposite to the beta-sheet encompassing the previously determined binding site for DAF, which implies that the adhesin can bind simultaneously to both receptors on the epithelial cell surface. The recognition of CEACAMs from a highly diverse DrCEA subfamily of Dr adhesins indicates that interaction with these receptors plays an important role in niche adaptation of E. coli strains expressing Dr adhesins.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington 98195-7242, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Korotkova
authors.forename: Ernesto
authors.initials: E
authors.lastname: Cota
authors.forename: Yuri
authors.initials: Y
authors.lastname: Lebedin
authors.forename: Severine
authors.initials: S
authors.lastname: Monpouet
authors.forename: Julie
authors.initials: J
authors.lastname: Guignot
authors.forename: Alain L
authors.initials: AL
authors.lastname: Servin
authors.forename: Steve
authors.initials: S
authors.lastname: Matthews
authors.forename: Steve L
authors.initials: SL
authors.lastname: Moseley
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D018958:CD55 Antigens / Q000737:chemistry / Q000502:physiology*; D016466:CHO Cells; D002272:Carcinoembryonic Antigen / Q000737:chemistry*; D002448:Cell Adhesion; D006224:Cricetinae; D004926:Escherichia coli / Q000378:metabolism*; D010861:Fimbriae, Bacterial / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D018829:Adhesins, Bacterial; D018958:CD55 Antigens; D002272:Carcinoembryonic Antigen