Rigden Daniel J, Galperin Michael Y, Jedrzejas Mark J
National Center of Genetic Resources and Biotechnology, Cenargen/Embrapa, Brasília, Brazil, D.F. 70770-900.
Crit Rev Biochem Mol Biol. 2003;38(2):143-68. doi: 10.1080/713609215.
Streptococcus pneumoniae is the most common cause of fatal community-acquired pneumonia, middle ear infection, and meningitis. The prevention and treatment of this infection have become a top priority for the medical-scientific community. The present polysaccharide-based vaccine used to immunize susceptible hosts is only approximately 60% effective and is ineffective in children younger than 2 years of age. The new conjugate vaccine, based on the engineered diphtheria toxin coupled to polysaccharide antigens. is approved only for use in children under 2 years of age to treat invasive disease. While penicillin is the drug of choice to treat infections secondary to S. pneumoniae, increasing numbers of bacterial strains are resistant to penicillin as well as to broad spectrum antibiotics such as vancomycin. Thus, there is a need to identify new strategies to prevent and treat diseases caused by to S. pneumoniae. In this article, we summarize the utilization of the recently available S. pneumoniae genomic information in order to identify and characterize novel proteins likely located on the surface of this Gram-positive pathogenic bacterium. Because only a limited number of surface proteins of S. pneumoniae have been characterized to date, this information provides new insights into the pathogenesis of this organism as well as highlights possible avenues for its treatment and/or prevention in the future. The review is divided into two sections. First, we brietly summarize current information about known surface-exposed proteins of S. pneumoniae. This is followed by the illustration of procedures for the identification of new putative surface-exposed proteins. These have signal peptides required for their extra-cytoplasmic transport and/or additional signature sequences. Some of these will be S. pneumoniae virulence factors. The signature sequences we have chosen are those leading to protein binding to choline present on the bacterial surface, attachment to peptidoglycan of the cell wall, or anchoring to lipids of the cytoplasmic membrane. All these signatures are indicative of binding of proteins to the surface of this organism. Secondly, we illustrate the application of bioinformatics and modeling tools to these selected proteins in order to provide information about their likely functions and preliminary three-dimensional structure models. The focal point of the analysis of these proteins, their sequences, and structures is the evaluation of their antigenic properties and possible roles in pathogenicity. The information obtained from the genome analysis will be instrumental in the development of a more effective prophylactic and/or therapeutic agents to prevent and to treat infections due to S. pneumoniae.
肺炎链球菌是致命的社区获得性肺炎、中耳感染和脑膜炎的最常见病因。这种感染的预防和治疗已成为医学科学界的首要任务。目前用于免疫易感宿主的基于多糖的疫苗的有效性仅约为60%，并且对2岁以下儿童无效。新型结合疫苗基于与多糖抗原偶联的工程化白喉毒素，仅被批准用于2岁以下儿童治疗侵袭性疾病。虽然青霉素是治疗肺炎链球菌继发感染的首选药物，但越来越多的菌株对青霉素以及万古霉素等广谱抗生素耐药。因此，需要确定预防和治疗肺炎链球菌所致疾病的新策略。在本文中，我们总结了最近可获得的肺炎链球菌基因组信息的利用情况，以便鉴定和表征可能位于这种革兰氏阳性病原菌表面的新型蛋白质。由于迄今为止仅鉴定了有限数量的肺炎链球菌表面蛋白，该信息为该生物体的发病机制提供了新见解，并突出了未来其治疗和/或预防的可能途径。本综述分为两个部分。首先，我们简要总结关于肺炎链球菌已知表面暴露蛋白的当前信息。接下来阐述鉴定新的假定表面暴露蛋白的程序。这些蛋白具有胞外转运所需的信号肽和/或其他特征序列。其中一些将是肺炎链球菌毒力因子。我们选择的特征序列是那些导致蛋白质与细菌表面存在的胆碱结合、附着于细胞壁肽聚糖或锚定到细胞质膜脂质的序列。所有这些特征都表明蛋白质与该生物体表面的结合。其次，我们阐述生物信息学和建模工具对这些选定蛋白质的应用，以便提供有关其可能功能和初步三维结构模型的信息。对这些蛋白质、其序列和结构分析的重点是评估其抗原特性和在致病性中的可能作用。从基因组分析获得的信息将有助于开发更有效的预防和/或治疗剂，以预防和治疗肺炎链球菌感染。
