EXTRACELLULAR SECRETION IN VIBRIO CHOLERAE

描述（改编自申请人的摘要）：霍乱毒素（CT），一种 由霍乱弧菌表达的肠毒素，为毒力因子 导致人类严重腹泻症状的病毒 从细菌中通过分泌机制编码，部分由染色体， EPS（胞外蛋白分泌）簇中的基因。 只有CT和A 少数其他周质蛋白质（蛋白酶和几丁质酶）由 eps系统，这表明，特定的运输信号识别的 分泌器位于每种蛋白质中。 PI和其他人 显示霍乱弧菌分泌CT和LT-IIa，这是一种由 大肠杆菌菌株，具有相同的效率。 自从B 细胞外转运必需的CT和LT-IIa多肽 共享很少，如果有的话，氨基酸同源性，这些上的转运信号， 毒素必须是保守的结构基序。 霍乱弧菌毒素分泌的分子机制研究 由于缺乏克隆的分泌复合物而受到阻碍。 第C、D、E、F、G、H段， I、J、K、L、M和N已被克隆，但基因簇不赋予 在E. coli分泌CT的能力。 这些数据表明， 需要基因来编码分泌机制。 也很可能 一种或多种Eps蛋白在物理水平上与CT相互作用 在运输过程中。 PI的目标是：1）研究 CT和LT-IIa中的细胞外转运信号; 2）表征 CC 9453是霍乱弧菌的一种突变体，缺乏 细胞外分泌;和3）确定哪些Eps蛋白具有 特异性CT结合活性。 目前还没有针对霍乱弧菌的长期有效疫苗。 直到疫苗 可用的替代策略，以改善疾病的症状 可能非常重要。 更好地理解这一过程 霍乱弧菌的细胞外分泌是霍乱治疗中必要的第一步。 随后设计治疗策略以改善霍乱症状 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.