IRON ACQUISITION AND PNEUMOCOCCAL INFECTION

铁的获取和肺炎球菌感染

• 批准号: 6453033
• 负责人: STANLEY S TAI
• 金额: $ 13.19万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6453033
• 关键词: Streptococcus pneumoniae; affinity chromatography; bacteria infection mechanism; bacterial proteins; binding proteins; centrifugation; gene mutation; heme; iron; laboratory mouse; molecular cloning; nucleic acid sequence; pathologic process; protein structure function; virulence; western blottings

Children under two years of age, the elderly, and individuals with underlying disease are to great risk of developing pneumococcal otitis media, septicemia, meningitis, and pneumonia. Antibiotic prophylaxis and vaccination are the two major methods to treat and prevent invasive pneumococcal infections. However, the success of antibiotic treatments has been limited by the recent isolation of penicillin-or multi-drug resistant pneumococci. The current pneumococcal vaccine, a mixture of capsular polysaccharide of 23 most prevalent of possible 84 stereotypes, only elicits type-specific antibodies and can not provide protection against infection of other Streptococcus pneumoniae serotypes not used in the vaccine preparation. To control pneumococcal disease would require a new knowledge about the biology of S. pneumoniae. The long range goal of this investigation is to study how S. pneumoniae survives in infected animals where most of iron molecules are sequestered by iron-binding proteins, such as hemoglobin, transferrin, and lactoferrin. Iron limitation restricted the growth of S. pneumoniae and the limited growth could be restored by the addition of hemin or hemoglobin. Pneumococcal cells have a great ability to bind hemin. Several hemin binding proteins have been identified in the cell lysate of S. pneumoniae with the major species migrated as a molecular mass of 43 kDa. The specific aims of this proposal are employing genetic and immunological methods to seek answers to the following question: 1). What is the genetic determinant of 43-kDa hemin binding protein? 2). What roles does 43-kDa HBP play in the hemin acquisition of S. pneumoniae? 3) What roles does 43-kDa HBP play in S. pneumoniae infection in experimental animals? Results generated from the proposed studies not only will provide us with basic information about the iron acquisition of S. pneumoniae, but will allow us to gain insight into the pathogenic mechanism of S. pneumoniae disease. The knowledge obtained in this study will have practical applications as well in designing effective therapeutic strategy and agents for the control of pneumococcal disease.

两岁以下的儿童、老年人和有 基础疾病极有可能发展为肺炎球菌性中耳炎 媒体、败血症、脑膜炎和肺炎。抗生素预防和 接种疫苗是治疗和预防入侵的两种主要方法 肺炎球菌感染。然而，抗生素治疗的成功已经 受到最近分离的青霉素耐药或多重耐药的限制 肺炎球菌。目前的肺炎球菌疫苗，是一种胶囊混合物 在84种可能的刻板印象中，最常见的23种多糖，仅 引起特定类型的抗体，不能提供保护 其他肺炎链球菌血清型感染未用于 疫苗准备工作。要控制肺炎链球菌疾病，需要一种新的 关于肺炎链球菌生物学的知识。这样做的长期目标是 调查是研究肺炎链球菌是如何在受感染的动物体内存活的。 大多数铁分子被铁结合蛋白隔离， 如血红蛋白、转铁蛋白和乳铁蛋白。铁限制 限制了肺炎链球菌的生长，限制了其生长。 通过添加氯化血红素或血红蛋白恢复的。肺炎球菌细胞有 很强的结合氯化血红素的能力。几种氯化血红素结合蛋白已经被 肺炎链球菌细胞裂解物中主要菌种的鉴定 以43 kDa的相对分子质量迁移。这项建议的具体目的 正在使用遗传和免疫学方法来寻找答案 以下问题：1)。43 kDa氯化血红素的遗传决定因素是什么 结合蛋白？2)。43-kDa HBP在氯化血红素中的作用 肺炎链球菌的获得性？3)43-kDa HBP在肺炎链球菌中起什么作用？ 实验动物的肺炎感染？生成的结果来自 拟议的研究不仅将为我们提供关于 铁获得肺炎链球菌，但将使我们获得洞察 肺炎链球菌病的致病机制。所获得的知识 本研究在设计中也将具有实际应用价值 控制肺炎链球菌的有效治疗策略和药物 疾病。