GENETIC ANALYSIS ACID RESISTANCE IN SHIGELLA SPECIES

简介(摘自申请者摘要)：志贺氏菌属 细菌性痢疾的病原体在肠道中是独一无二的 疾病所需的低感染剂量的病原体。然而，在 10(E)生产6种霍乱弧菌或10(E)5种沙门氏菌 在疾病方面，500种或更少的志贺氏菌能够做到这一点。全 肠道病原体必须突破胃部的酸性屏障 才能到达肠道。最近的研究表明， 志贺氏菌感染剂量低的原因是这些生物 比其他肠道细菌更能在酸性环境中生存 病原体。尽管对志贺氏菌如何存活的理解 酸性环境将增加我们对发病机制的了解，这 研究也可能对LIVE的发展产生重大影响 口服疫苗。口服疫苗必须大剂量和 用碳酸氢钠注射以确保有效剂量 进入肠道。拟议的研究可能会导致 构建更少的耐酸口服疫苗菌株 生产成本高，管理更简单，效果更好。 志贺氏菌病仅限于人类和高等灵长类动物 检验感染剂量与酸的关系是不切实际的。 动物模型中的抵抗力。鼠伤寒沙门氏菌是一种自然致病菌。 然而，这一假说很容易在老鼠身上得到检验。 本研究的具体目标是：1)鉴定志贺氏菌基因， 以及与在酸性环境中生存能力有关的基因产品 利用分子生物学技术。2)构建一种耐酸的 导入志贺氏菌属耐酸基因的鼠伤寒沙门氏菌 进入鼠伤寒沙门氏菌。

DESCRIPTION (Adapted from applicant's abstract): Shigella species, the causative agents of bacillary dysentery, are unique among enteric pathogens in the low infective dose required for disease. Whereas over 10(e)6 Vibrio cholera or 10(e)5 Salmonella species are required to produce disease, five hundred or less Shigella species are able to do so. All enteric pathogens must breach the acid barrier encountered in the stomach in order to reach the intestines. Recent research suggests that one explanation for the Shigella's low infective dose is that these organisms are better able to survive in an acidic environment than are other enteric pathogens. Although an understanding of how Shigella species survive an acidic environment will add to our knowledge of pathogenesis, this research could also have a significant impact on the development of live oral vaccines. Oral vaccines must be given in high dosage and administered with sodium bicarbonate to insure that an effective dose enters the intestines. The proposed research could lead to the construction of acid-resistant, oral vaccines strains which would be less costly to produce, simpler to administer, and more efficacious. The fact that shigellosis is confined to humans and higher primates make it impractical to test the relationship between infective dose and acid resistance in an animal model. S. typhimurium is a natural pathogen in mice however and this hypothesis could readily be tested in mice. The specific goals of this research are: 1) To identify Shigella genes, and gene products involved in the ability to survive an acidic environment using techniques of molecular biology. 2) To construct an acid resistant S. typhimurium by transferring acid resistant genes from Shigella species into S. typhimurium.