Streptococcus pneumoniae (S. pneumoniae) is an important pathogen worldwide that causes pneumococcal infections which are related to high rates of morbidity and mortality especially in young children, older adults, and immune-compromised persons. Antibiotic resistance in S. pneumoniae is a serious problem across the world from time to time, resulting in treatment failure and diminished value of older medicines. Therefore, the objective of this study was to identify new putative drug targets against S. pneumoniae serotype 23F by using subtractive genomics. By using bioinformatics tools such as NCBI, UniProt KB, PDB, KEGG, DEG, PSORTb, CD hit, DrugBank database, and other softwares, proteins involved in unique metabolic pathways of S. pneumoniae serotype 23F were studied. The result indicates that this serotype consists of 97 metabolic pathways of which 74 are common with that of human, and 23 pathways are unique to the serotype 23F. After investigation and analysis of essentiality, nonhomology, subcellular localization, having drug targets, and enzymatic activity, four proteins were prioritized as druggable targets. These druggable proteins include UDP-N-acetylglucosamine 1-carboxyvinyltransferase, UDP-N-acetyl muramate dehydrogenase, D-alanine-D-alanine ligase, and alanine racemase that are found in S. pneumoniae serotype 23F. All these four proteins are essential, are nonhomologous with human proteins, have drug targets, and are located in cell cytoplasm. Therefore, the authors recommend these proteins to be used for efficient drug design against S. pneumoniae serotype 23F after experimental validation for essentiality and druggability.

中文翻译：

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通过消减基因组学对肺炎链球菌 ATCC 700669（血清型 23F）中的药物靶标进行计算机模拟鉴定和表征

肺炎链球菌（S.pneumoniae）是世界范围内引起肺炎球菌感染的重要病原体，肺炎球菌感染与高发病率和死亡率有关，特别是在幼儿、老年人和免疫功能低下的人群中。肺炎链球菌的抗生素耐药性时常成为世界范围内的一个严重问题，导致治疗失败和旧药物的价值下降。因此，本研究的目的是通过使用消减基因组学来确定针对肺炎链球菌血清型 23F 的新的假定药物靶点。利用NCBI、UniProt KB、PDB、KEGG、DEG、PSORTb、CD hit、DrugBank数据库等生物信息学工具，对肺炎链球菌血清型23F独特代谢途径涉及的蛋白质进行研究。结果表明，该血清型由97条代谢途径组成，其中74条是人类共有的，23条是23F血清型所特有的。经过对必要性、非同源性、亚细胞定位、药物靶点和酶活性的调查和分析，四种蛋白质被优先作为可药物靶点。这些可药物蛋白包括 UDP-N-乙酰葡糖胺 1-羧基乙烯基转移酶、UDP-N-乙酰胞壁酸脱氢酶、D-丙氨酸-D-丙氨酸连接酶和丙氨酸消旋酶，这些酶存在于S. 肺炎链球菌血清型23F。所有这四种蛋白质都是必需的，与人类蛋白质非同源，具有药物靶标，并且位于细胞的细胞质中。因此，作者建议将这些蛋白质用于针对金黄色葡萄球菌的有效药物设计。经过必要性和成药性实验验证后的肺炎链球菌血清型 23F。