SHIGELLA

志贺氏菌

• 批准号: 6449028
• 负责人: THOMAS G CLEARY
• 金额: $ 17.64万
• 依托单位: EASTERN VIRGINIA MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6449028
• 关键词: Escherichia coli; HeLa cells; Salmonella; Shigella; Shigella dysenteriae; antibacterial antibody; bacillary dysentery; bactericidal immunity; breast feeding; clinical research; cross immunity; developmental nutrition; enterotoxins; glycolipids; human milk; human subject; infant human (0-1 year); laboratory rabbit; lactoferrin; nutrition related tag; plasmids; secretory immune system; tissue /cell culture; virulence

Human milk provides antibodies and non-antibody factors that may account for breast feeding protecting from symptomatic shigellosis. Virulence mechanisms of Shigella spp are shared with other enteropathogens. This proposal addresses the relationship between shared mechanisms of virulence and human milk factors that interact with these shared factors. We hypothesize that human milk factors which protect against Shigella spp. also provides protection against other enteropathogens that express related virulence proteins. The specific aims address both sigA and non IgA protective factors. Aim 1. Define the role of anti-invasion plasmid antigen [anti-IPA] antibodies in protection from shigellosis by determining the relationship between quantity of milk antibodies to baculovirus expressed recombinant IpaB, IpaC and IpaD in human milk and symptom status of breast-fed infants who become infected with Shigella spp. Aim 2. Define the role of cross protective anti-Ipa sigA by characterizing human milk antibodies directed toward invasion plasmid antigen epitopes shared by Shigella spp., invasive E. coli (EIEC) and Salmonella spp. Aim 3. Define the role of human milk antibodies to shigatoxin produced by S. dysenteriae serotype 1 by characterizing the ability of isolated affinity purified anti-B subunit sIgA derived from human milk to block toxin-induced HeLa cell cytotoxicity and accumulation of hemorrhagic fluid in rabbit ileal loops. Aim 4. Determine the role of non-antibody milk factors (anti-inflammatory [cytokine binding] factors, lactoferrin, shigatoxin-binding glycolipids) which interact with Shigella spp. virulence factors in tissue culture (HeLa cell invasion) and animal models (rabbit enteritis and rabbit ligated ileal loop) of pathogenesis.

母乳提供抗体和非抗体因子，可能会导致 用于母乳喂养，预防有症状的志贺氏菌病。毒力 志贺氏菌的机制与其他肠道病原体相同。这 提案解决了共享毒力机制之间的关系 以及与这些共同因素相互作用的母乳因素。我们 假设母乳因子可以预防志贺氏菌。 还提供针对表达的其他肠道病原体的保护 相关毒力蛋白。具体目标涉及 sigA 和非 IgA 保护因素。目的1.明确抗侵袭质粒的作用 抗原 [抗 IPA] 抗体可预防志贺氏菌病 确定乳汁抗体数量与 杆状病毒在人乳中表达重组 IpaB、IpaC 和 IpaD 感染志贺氏菌的母乳喂养婴儿的症状状况 种。目标 2. 通过以下方式定义交叉保护性抗 Ipa sigA 的作用： 表征针对入侵质粒的人乳抗体 志贺氏菌属、侵袭性大肠杆菌 (EIEC) 和 沙门氏菌属目标 3. 定义母乳抗体的作用 志贺毒素由痢疾杆菌血清型 1 产生，通过表征 分离的亲和纯化抗 B 亚基 sIgA 的能力 母乳可阻断毒素诱导的 HeLa 细胞的细胞毒性和积累 兔回肠环中的出血液。目标 4. 确定角色 非抗体乳因子（抗炎[细胞因子结合]因子， 与志贺氏菌相互作用的乳铁蛋白、志贺毒素结合糖脂） 种。组织培养（HeLa 细胞侵袭）和动物中的毒力因子 发病机制模型（兔肠炎和兔回肠结扎）。