Molecular analysis of pneumococcal disease

肺炎链球菌(肺炎球菌)是一种重要的人类病原体，每年在发展中国家导致数百万儿童死亡。肺炎球菌病的高发病率和死亡率也因这种微生物对多种抗生素产生抗药性的速度而加剧。现有的肺炎球菌多糖疫苗对幼儿的免疫原性较差，仅针对有限范围的血清型提供保护。目前正在开发的更具免疫原性的结合疫苗的血清型覆盖率甚至更低；这些疫苗也将非常昂贵，从而限制了它们在发展中国家的使用，因为发展中国家最需要有效的儿科疫苗。肺炎球菌产生多种在致病过程中起重要作用的蛋白质，但这些因素在感染过程每个阶段的相对贡献仍有待确定。此外，对这些毒力因子如何对细菌的外部环境做出反应的机制几乎一无所知。有鉴于此，我们正在对肺炎球菌疾病的发病机制进行全面的研究，特别是参考假定的毒力蛋白的作用。这些信息正被用于开发基于所有血清型通用的肺炎球菌蛋白抗原的廉价而有效的疫苗。

Streptococcus pneumoniae (the pneumococcus) is an important human pathogen, which is responsible for the deaths of millions of children each year in developing countries. The high morbidity and mortality associated with pneumococcal disease is also being exacerbated by the rate at which this organism is acquiring resistance to multiple antibiotics. Existing pneumococcal polysaccharide vaccines are poorly immunogenic in young children and only provide cover against a limited range of serotypes. Serotype coverage is even lower in the more immunogenic conjugate vaccines currently being developed; these will also be very expensive, thereby limiting their use in developing countries, where the need for effective paediatric vaccines is greatest. Pneumococci produce a variety of proteins which are important in causing disease, but the relative contribution of these factors at each stage of the infection process remain to be determined. Moreover, virtually nothing is known of the mechanism whereby these virulence factors are regulated in response to the external environment of the bacterium. In view of this, we are conducting a comprehensive examination of the mechanisms of pathogenesis of pneumococcal disease, with particular reference to the role of putative virulence proteins. This information is being used to develop cheap and effective vaccines based on pneumococcal protein antigens common to all serotypes.