HAEMOPHILUS INFLUENZAE B VIRULENCE: ROLE OF HAEMOCIN

B 型流感嗜血杆菌毒力：血红素的作用

• 批准号: 3455354
• 负责人: JOHN J LIPUMA
• 金额: $ 10.78万
• 依托单位: ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3455354
• 关键词: Haemophilus influenzae; antibacterial antibody; bacterial cytopathogenic effect; bacterial genetics; bacterial meningitis; bacterial proteins; bacteriocin; child (0-11); disease /disorder model; electron microscopy; enzyme linked immunosorbent assay; gene mutation; genetic library; genetic strain; histopathology; human tissue; infant animal; laboratory rat; molecular cloning; nucleic acid sequence; protein purification; protein structure function; recombinant DNA; respiratory epithelium; transposon /insertion element; vascular endothelium; virulence; western blottings

DESCRIPTION (Adapted from applicant's abstract): H. influenzae is a human-specific bacterial pathogen responsible for a variety of serious infections in children, including pneumonia, cellulitis, septic arthritis, and epiglottitis. Further, H. influenzae is the most common cause of bacterial meningitis in the United States, affecting approximately 12,000 children annually. Despite recent advances in antimicrobial therapy, the morbidity and mortality resulting from H. influenzae infection has changed little during the past decade. Two factors clearly distinguish strains of H. influenzae which cause invasive infection from relatively avirulent members of this species: the presence of polysaccharide capsule composed of polyribosyl ribitol phosphate (PRP) and the production of a bacteriocin protein termed haemocin. Whereas the PRP capsule has been extensively examined as a virulence factor, the role of haemocin has not been investigated. This proposal seeks to investigate the role of haemocin in the virulence of H. influenzae. To unambiguously define this role, the genetic basis of haemocin production will be determined, and the gene(s) encoding haemocin will be cloned. Mutagenesis of the cloned haemocin gene will be performed to construct isogeneic strains of H. influenzae differing only in their ability to produce haemocin. These isogeneic strains will then be used to determine the effect of haemocin production in virulence by using a relevant animal model of H. influenzae infection. The relative abilities of HMC+ and HMC-strains to colonize and to invade infant rats will be assessed. Another goal of this project is to purify and characterize the haemocin protein. The potential role of haemocin in contributing to virulence by mediating a direct toxic effect upon mammalian host cells will be examined by investigating the effects of haemocin production upon relevant human tissue in vitro. Should haemocin prove important in virulence, the availability of the cloned haemocin gene and its protein product will permit further investigations designed to define new strategies for the prevention of H. influenzae infection.

描述（改编自申请人的摘要）：H。流感是一个 人类特异性细菌病原体负责多种严重 儿童感染，包括肺炎，蜂窝织炎，化粪池关节炎， 和上皮炎。 此外，流感h。是最常见的原因 美国细菌性脑膜炎，影响约12,000 每年的孩子。 尽管最近在抗菌治疗方面取得了进步，但 流感感染引起的发病率和死亡率已经改变 在过去的十年中很少。 两个因素显然区分了菌株 H.流感，引起相对无毒的侵入性感染 该物种的成员：组成多糖胶囊的存在 多氧蛋白核糖核醇磷酸盐（PRP）和细菌素的产生 蛋白质称为血红蛋白。 prp胶囊已广泛 被检查为毒力因子，血红蛋白的作用尚未 调查。 该提议旨在研究血红蛋白在毒力中的作用 H.流感。 为了明确定义这一角色， 将确定血红蛋白的产生，并编码血红蛋白的基因 将被克隆。 克隆血红蛋白基因的诱变将进行 构建流感h。H. 产生血红素的能力。 这些亚系菌株将用于 通过使用A来确定血红蛋白产生在毒力中的影响 流感h。感染的相关动物模型。 相对能力 HMC+和HMC-strains的定殖和入侵婴儿大鼠的 评估。 该项目的另一个目标是净化和表征 血红蛋白蛋白。 血红蛋白在促进的潜在作用 通过介导对哺乳动物宿主细胞的直接毒性作用来毒力将 通过研究血红蛋白的产生对 相关的人体组织体外。 血红蛋白应该在 毒力，克隆血红蛋白基因及其蛋白的可用性 产品将允许旨在定义新的进一步调查 预防流感h。感染的策略。