A subfamily of Dr adhesins of Escherichia coli bind independently to decay-accelerating factor and the N-domain of carcinoembryonic antigen.
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.
Korotkova
Natalia
N
Department of Microbiology, University of Washington, Seattle, Washington 98195-7242, USA.
Cota
Ernesto
E
Lebedin
Yuri
Y
Monpouet
Severine
S
Guignot
Julie
J
Servin
Alain L
AL
Matthews
Steve
S
Moseley
Steve L
SL
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
D018829:Adhesins, Bacterial; D018958:CD55 Antigens; D002272:Carcinoembryonic Antigen