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“艰难梭菌”感染（经常与抗生素治疗相关）是在全世界医院中正在快速发展的一种危险。该细菌产生两种毒素：A和B，用纯化的毒素所做研究使人们产生这样一个共同的认识：毒素A是致病的主要原因。 现在，一项新的研究（在该研究中，研究人员用缺乏每种毒素的细菌菌种在一个动物模型上进行试验）表明，事实上毒素B是“艰难梭菌”毒力所必需的，并且可能是治疗或预防措施的一个更有希望的潜在目标。 推荐原始出处： Nature 458, 1176-1179 (30 April 2009) | doi:10.1038/nature07822 Toxin B is essential for virulence of Clostridium difficile Dena Lyras1, Jennifer R. O'Connor1,3, Pauline M. Howarth1, Susan P. Sambol3, Glen P. Carter1, Tongted Phumoonna1, Rachael Poon1,2, Vicki Adams1, Gayatri Vedantam3, Stuart Johnson3, Dale N. Gerding3 & Julian I. Rood1,2 1 Australian Bacterial Pathogenesis Program and, 2 Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Department of Microbiology, Monash University, Victoria 3800, Australia 3 Medical Service and Research Service, Hines VA Hospital, Hines, Illinois 60141, USA, and Infectious Disease Section, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, USA Clostridium difficile is the leading cause of infectious diarrhoea in hospitals worldwide, because of its virulence, spore-forming ability and persistence1, 2. C. difficile-associated diseases are induced by antibiotic treatment or disruption of the normal gastrointestinal flora3, 4. Recently, morbidity and mortality resulting from C. difficile-associated diseases have increased significantly due to changes in the virulence of the causative strains and antibiotic usage patterns1, 2, 5, 6. Since 2002, epidemic toxinotype III NAP1/027 strains1, 2, which produce high levels of the major virulence factors, toxin A and toxin B, have emerged. These toxins have 63% amino acid sequence similarity7 and are members of the large clostridial glucosylating toxin family, which are monoglucosyltransferases that are pro-inflammatory, cytotoxic and enterotoxic in the human colon8, 9, 10. Inside host cells, both toxins catalyse the transfer of glucose onto the Rho family of GTPases, leading to cell death8, 11. However, the role of these toxins in the context of a C. difficile infection is unknown. Here we describe the construction of isogenic tcdA and tcdB (encoding toxin A and B, respectively) mutants of a virulent C. difficile strain and their use in the hamster disease model to show that toxin B is a key virulence determinant. Previous studies showed that purified toxin A alone can induce most of the pathology observed after infection of hamsters with C. difficile 8, 9, 12 and that toxin B is not toxic in animals unless it is co-administered with toxin A, suggesting that the toxins act synergistically12. Our work provides evidence that toxin B, not toxin A, is essential for virulence. Furthermore, it is clear that the importance of these toxins in the context of infection cannot be predicted exclusively from studies using purified toxins, reinforcing the importance of using the natural infection process to dissect the role of toxins in disease. (责任编辑：Doctor001) |
