Towards a Structural Basis for the Relationship Between Blood Group and the Severity of El Tor Cholera**
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چکیده
Diarrheal diseases caused by Vibrio cholerae and enterotoxigenic E. coli (ETEC) lead to millions of deaths each year. The protein toxins produced by these bacteria are 80% identical and comprise a single toxic A-subunit associated with a pentamer of B-subunits. The B-pentamer enables the toxin to enter cells by first binding to the ganglioside GM1 glycolipid 1 (Figure 1a,b). Inhibitors of this binding event are therefore potential anti-diarrheal drugs. The severity of cholera caused by the El Tor biotype of V. cholerae is known to be blood-group dependent; people in blood group O are affected more severely than those in blood groups A or B. In contrast, there is no clear blood-group dependence for theV. choleraeO1 classical biotype, and any similar correlation for ETEC-related diarrhoea is a matter of dispute. The A, B and O blood groups are distinguished by carbohydrates present on the surface of cells. For example, blood group O is characterized by oligosaccharides terminating in a 2-O-fucosyl-galactose structure (e.g. 5), the so-called H-antigen. In blood groups A and B, the H-antigen is further substituted by an a-galactosamine or galactose residue, respectively (e.g., 3a and 4). There have been several reports that the cholera toxin Bsubunit (CTB) does not bind to blood group oligosaccharides; however, most binding studies appear to have been undertaken using classical biotype CTB, rather than El Tor CTB. In contrast, the heat-labile toxin B-subunit (LTBh) is reported to bind to both blood group A and B oligosaccharides with similar affinity, but not to H-antigen oligosaccharides. Blood group A oligosaccharide 3b has been crystal-
منابع مشابه
Technical considerations of cholera vaccines and some results of cholera - El-Tor mass immunization
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