Blood group antigen recognition by Escherichia coli heat-labile enterotoxin.
In a number of bacterial infections, such as Helicobacter pylori, Campylobacter jejuni and Vibrio cholerae infections, a correlation between the severity of disease and blood group phenotype of infected individuals has been observed. In the present investigation, we have studied the molecular basis of this effect for enterotoxigenic Escherichia coli (ETEC) infections. ETEC are non-invasive bacteria, which act through second messenger pathways to cause diarrhea. It has been suggested that the major virulence factor of ETEC from human isolates, i.e. the human heat-labile enterotoxin (hLT), recognizes certain blood group epitopes, although the molecular basis of blood group antigen recognition is unknown. The 2.5 A crystal structure of the receptor-binding B-subunit of hLT in complex with the blood group A antigen analog GalNAcalpha3(Fucalpha2)Galbeta4(Fucalpha3)Glcbeta provides evidence of a previously unknown binding site in the native toxin. The structure reveals the molecular interactions underlying blood group antigen recognition and suggests how this protein can discriminate between different blood group epitopes. These results support the previously debated role of hLT in the blood group dependence of ETEC infections. Similar observations regarding the closely related cholera toxin in V. cholera infections are also discussed.
Holmner
Asa
A
Department of Chemistry and Bioscience, Chalmers University of Technology, PO box 462, SE-40530 Göteborg, Sweden.
Askarieh
Glareh
G
Okvist
Mats
M
Krengel
Ute
U
D000595:Amino Acid Sequence; D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D001789:Blood Group Antigens / Q000378:metabolism*; D050260:Carbohydrate Metabolism; D018360:Crystallography, X-Ray; D004768:Enterotoxins / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D016415:Sequence Alignment; D013499:Surface Properties
D001427:Bacterial Toxins; D001789:Blood Group Antigens; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C027538:heat-labile enterotoxin, E coli