IRON ACQUISITION AND PNEUMOCOCCAL INFECTION

2岁以下儿童、老年人和患有 基础疾病是发展为肺炎球菌性耳炎的巨大风险 中、败血症、脑膜炎和肺炎。抗生素预防和 疫苗接种是治疗和预防侵袭性疾病的两种主要方法。 肺炎球菌感染然而，抗生素治疗的成功 受到最近分离出的青霉素或多药耐药菌的限制， 肺炎球菌。目前的肺炎球菌疫苗，一种混合物， 多糖的23个最普遍的可能84定型，只有 抗体，并且不能提供针对 感染其他肺炎链球菌血清型， 疫苗制备。要控制肺炎球菌疾病， 了解S.肺炎。长期目标是 调查的目的是研究S.肺炎病毒在受感染的动物体内存活 其中大部分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S.肺炎和有限的增长可能是 通过加入氯化血红素或血红蛋白而恢复。肺炎球菌细胞具有 结合氯化血红素的能力很强几种氯化血红素结合蛋白已经被 在S.肺炎与主要种属 分子量为43 kDa。本提案的具体目标 正在使用遗传学和免疫学方法来寻找答案， 问题：1）。什么是43 kDa氯化血红素的遗传决定因素 结合蛋白？2）。43-kDa HBP在氯化血红素中起什么作用 收购S。肺炎？3)43-kDa HBP在S. 实验动物感染肺炎？结果生成自 拟议的研究不仅将为我们提供有关 铁收购S.肺炎，但将使我们能够深入了解 对S.肺炎疾病。获得的知识 这项研究将有实际应用，以及在设计 控制肺炎球菌感染的有效治疗策略和药物 疾病

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.