MOLECULAR BIOLOGY AND VIRULENCE OF CTX PHAGE

描述（改编自申请人的摘要）：霍乱毒素是 革兰氏阴性菌霍乱弧菌的主要毒力因子 导致严重的霍乱 调查人员 最近发现，这种强效肠毒素是由一种新的 命名为CTX的丝状噬菌体。 CTX噬菌体是第一个 已知导致宿主溶原性转化的丝状噬菌体 细菌。 CTX噬菌体可以整合到霍乱弧菌染色体中， 形成稳定的溶原细胞，或在诱导后从染色体上切除， 作为质粒复制。 在噬菌体的复制阶段 霍乱毒素可以独立于生命周期中的因子表达， 这被认为是其表达所必需的。 我们的演示 从宿主内溶胆弧菌诱导CTX噬菌体 胃肠道提示体内CTX噬菌体 诱导在霍乱弧菌的毒力中起重要作用。 拟议研究的目标是了解 在分子水平上的CTX噬菌体，并评估其意义， 噬菌体在霍乱发病机制中的作用。 这些研究将建立 毒力水平转移机制的分子生物学 基因，从而进一步了解病原体的出现。 研究肠内诱导溶原细胞产生的CTX噬菌体， 建立一个新的范式来理解表达的调节 噬菌体编码的各种细菌病原体的毒力因子， 被转化噬菌体溶原化。 这项工作也将具有重要意义。 安全性更高的霍乱弧菌减毒活疫苗的设计 菌株

DESCRIPTION (Adapted from the applicant's abstract): Cholera toxin is the principal virulence factor of Vibrio cholerae, the Gram-negative bacterium that causes the severe diarrheal disease cholera. The investigators recently discovered that this potent enterotoxin is encoded by a novel filamentous bacteriophage designated CTX. The CTX phage is the first filamentous phage known to result in the lysogenic conversion of a host bacterium. The CTX phage can integrate into the V. cholerae chromosome and form stable lysogens or, after induction, excise from the chromosome and replicate as a plasmid. During this replicative stage of the phage life-cycle, cholera toxin can be expressed independently of the factors which were believed to be essential for its expression. Our demonstration of the induction of CTX phage from V. cholerae lysogens within the host gastrointestinal tract suggests the possibility that in vivo CTX phage induction plays a significant role in the virulence of V. cholerae. The objectives of the proposed studies are to understand the life-cycle of the CTX phage at the molecular level and to assess the significance of this bacteriophage in the pathogenesis of cholera. These studies will establish the molecular biology of a mechanism of horizontal transfer of virulence genes and thereby further our understanding of the emergence of pathogens. The study of the intraintestinal induction of CTX phage from lysogens, could establish a new paradigm for understanding the regulation of the expression of phage encoded virulence factors in a variety of bacterial pathogens that are lysogenized with converting phage. This work will also have important ramifications for the design of safer live attenuated V. cholerae vaccine strains.