EXTRACELLULAR SECRETION IN VIBRIO CHOLERAE

描述(摘自申请人摘要)：霍乱毒素(CT)， 霍乱弧菌表达的致病因子--肠毒素 导致人类出现严重腹泻症状的人获释 通过部分由染色体编码的分泌机制从细菌中分离出来 EPS(细胞外蛋白分泌)簇中的基因。只有CT和A 几乎没有其他周质蛋白(蛋白酶和几丁质酶)是由 EPS系统，表明特定的传输信号由 分泌器官位于每种蛋白质中。公安党和其他人 霍乱弧菌分泌CT和LT-IIa，这是一种由霍乱弧菌产生的肠毒素 大肠杆菌菌株，具有相同的效率。因为B 胞外转运必需的CT和LT-IIa多肽 如果有，氨基酸同源性很少，这些细胞上的运输信号 毒素必须是保守的结构基序。 霍乱弧菌毒素分泌的分子方面的研究包括 由于缺乏克隆的分泌物复合体而受阻。EPS C、D、E、F、G、H I、J、K、L、M和N已经被克隆，但基因簇不能提供 在大肠杆菌中产生分泌CT的能力。这些数据表明， 基因是对分泌机制进行编码所必需的。它也有可能是 一个或多个EPS蛋白与CT在物理水平上相互作用 在运输过程中。 PI的目标是：1)研究分子的分子结构 CT和LT-IIa的胞外转运信号；2)表征 霍乱弧菌突变株CC9453的遗传损伤 细胞外分泌；以及3)确定哪些EPS蛋白具有 特异性CT结合活性。 目前还没有长期有效的霍乱疫苗。直到疫苗问世 可用于改善疾病症状的替代策略 可能是非常重要的。更好地理解这一过程 霍乱弧菌的胞外分泌是霍乱弧菌感染的必要第一步 随后设计改善霍乱症状的治疗策略 通过抑制CT的释放。

DESCRIPTION (Adapted from the applicant's abstract): Cholera toxin (CT), an enterotoxin expressed by Vibrio cholerae that is the virulence factor responsible for eliciting severe diarrheal symptoms in humans is released from the bacterium by a secretory mechanism encoded, in part, by chromosomal genes in the eps (extracellular protein secretion) cluster. Only CT and a few other periplasmic proteins (protease and chitinase) are secreted by the eps system, suggesting that specific transport signals recognized by the secretory apparatus are located in each protein. The PI and others have shown that V. cholerae secretes CT and LT-IIa, an enterotoxin produced by strains of Escherichia coli, with equal efficiency. Since the B polypeptides of CT and LT-IIa that are essential for extracellular transport share little, if any, amino acid homology, the transport signals on these toxins must be conserved structural motifs. Studies on the molecular aspects of toxin secretion by V. cholerae are hampered by the lack of a cloned secretion complex. Eps C, D, E, F, G, H, I, J, K, L, M, and N have been cloned, but the gene cluster does not confer upon E. coli the ability to secrete CT. These data suggest that additional genes are required to encode the secretion machinery. It is also likely that one or more of the Eps proteins interacts with CT on a physical level during transport. The PI's goals are: 1) to investigate the molecular structure of the extracellular transport signals in CT and LT-IIa; 2) to characterize the genetic lesion in CC9453, a mutant of V. cholerae that is deficient in extracellular secretion; and 3) to determine which of the Eps proteins have specific CT-binding activity. There is no longterm, effective vaccine for V. cholera. Until a vaccine is available, alternative strategies to ameliorate the symptoms of the disease are potentially very important. A better understanding of the process of extracellular secretion by V. cholerae is a necessary first step in the subsequent design of therapeutic strategies to ameliorate cholera symptoms by inhibiting release of CT.