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首页> 外文期刊>Critical Reviews in Biochemistry and Molecular Biology >Analysis of structure and function of putative surface-exposed proteins encoded in the Streptococcus pneumoniae genome: A bioinformatics-based approach to vaccine and drug design [Review]
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Analysis of structure and function of putative surface-exposed proteins encoded in the Streptococcus pneumoniae genome: A bioinformatics-based approach to vaccine and drug design [Review]

机译：肺炎链球菌基因组中编码的假定表面暴露蛋白的结构和功能分析：基于生物信息学的疫苗和药物设计方法[综述]

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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 similar to60% 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 briefly 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. [References: 141]
机译：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原因。预防和治疗这种感染已成为医学界的当务之急。目前用于免疫易感宿主的基于多糖的疫苗仅对60％有效，对2岁以下的儿童无效。基于结合了多糖抗原的工程白喉毒素的新型结合疫苗，仅被批准用于2岁以下的儿童，以治疗侵袭性疾病。尽管青霉素是治疗继发于肺炎链球菌的感染的首选药物，但越来越多的细菌菌株对青霉素以及广谱抗生素（例如万古霉素）具有抗性。因此，需要确定预防和治疗由肺炎链球菌引起的疾病的新策略。在本文中，我们总结了最近可利用的肺炎链球菌基因组信息的利用，以鉴定和鉴定可能位于该革兰氏阳性病原菌表面的新型蛋白质。由于迄今为止仅表征了有限数量的肺炎链球菌表面蛋白，因此该信息为该生物的发病机理提供了新的见识，并突出了其未来治疗和/或预防的可能途径。该评论分为两个部分。首先，我们简要概述有关已知的肺炎链球菌表面暴露蛋白的最新信息。接下来是鉴定新的假定的表面暴露蛋白的程序的说明。这些具有其胞质外转运和/或其他标记序列所需的信号肽。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上存在的胆碱结合，与细胞壁肽聚糖结合或锚定至细胞质膜脂质的序列。所有这些特征表明蛋白质与该生物体表面的结合。其次，我们说明了生物信息学和建模工具在这些选定蛋白质上的应用，以提供有关其可能功能和初步三维结构模型的信息。这些蛋白质，其序列和结构的分析重点是对其抗原特性及其在致病性中可能作用的评估。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引起的感染。 [参考：141]

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