Ganeshapillai Jeyabarathy, Vinogradov Evguenii, Rousseau Joyce, Weese J Scott, Monteiro Mario A
Department of Chemistry, University of Guelph, Guelph, ON, Canada N1G 2W1.
Carbohydr Res. 2008 Mar 17;343(4):703-10. doi: 10.1016/j.carres.2008.01.002. Epub 2008 Jan 12.
Clostridium difficile is a Gram-positive bacterium that is known to be a cause of enteric diseases in humans. It is the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis. Recently, large outbreaks of C. difficile-associated diarrhea have been reported internationally, and there have been reports of increases in severe disease, mortality and relapse rates. At the moment, there is no vaccine against C. difficile, and the medical prevention of C. difficile infection is mostly based on the prophylactic use of antibiotics; however, this has led to an increase in the incidence of the disease. Here, we describe the chemical structure of C. difficile cell-surface polysaccharides. The polysaccharides of three C. difficile strains were structurally analyzed; ribotype 027 (North American pulsotype 1) strain was observed to express two polysaccharides, one was composed of a branched pentaglycosyl phosphate repeating unit: [-->4)-alpha-l-Rhap-(1-->3)-beta-D-Glcp-(1-->4)-[alpha-l-Rhap-(1-->3]-alpha-D-Glcp-(1-->2)-alpha-D-Glcp-(1-->P] and the other was composed of a hexaglycosyl phosphate repeating unit: [-->6)-beta-D-Glcp-(1-->3)-beta-D-GalpNAc-(1-->4)-alpha-D-Glcp-(1-->4)-[beta-D-Glcp-(1-->]-beta-D-GalpNAc-(1-->3)-alpha-D-Manp-(1-->P]. The latter polysaccharide was also observed to be produced by strains MOH900 and MOH718. The results described here represent the first literature report describing the covalent chemical structures of C. difficile cell-surface polysaccharides, of which PS-II appears to be a regular C. difficile antigen. These C. difficile teichoic-acid-like polysaccharides will be tested as immunogens in vaccine preparations in a rat and horse model.
艰难梭菌是一种革兰氏阳性细菌，已知是人类肠道疾病的病因。它是抗生素相关性腹泻和伪膜性结肠炎的主要原因。最近，国际上报道了多起艰难梭菌相关性腹泻的大规模暴发，并且有报道称严重疾病、死亡率和复发率有所增加。目前，尚无针对艰难梭菌的疫苗，艰难梭菌感染的医学预防主要基于抗生素的预防性使用；然而，这导致了该疾病发病率的上升。在此，我们描述了艰难梭菌细胞表面多糖的化学结构。对三株艰难梭菌菌株的多糖进行了结构分析；观察到核糖体分型027（北美脉冲型1）菌株表达两种多糖，一种由分支的五糖基磷酸重复单元组成：[→4)-α-L-鼠李糖-(1→3)-β-D-葡萄糖-(1→4)-[α-L-鼠李糖-(1→3]-α-D-葡萄糖-(1→2)-α-D-葡萄糖-(1→P]，另一种由六糖基磷酸重复单元组成：[→6)-β-D-葡萄糖-(1→3)-β-D-氨基半乳糖-(1→4)-α-D-葡萄糖-(1→4)-[β-D-葡萄糖-(1→]-β-D-氨基半乳糖-(1→3)-α-D-甘露糖-(1→P]。还观察到菌株MOH900和MOH718也产生后一种多糖。此处描述的结果代表了首篇描述艰难梭菌细胞表面多糖共价化学结构的文献报道，其中PS-II似乎是一种常见的艰难梭菌抗原。这些艰难梭菌类磷壁酸多糖将在大鼠和马模型中作为疫苗制剂中的免疫原进行测试。
