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通过反向疫苗学鉴定肺炎链球菌中的蛋白质及其在临床分离株中的遗传多样性。

Identification of proteins in Streptococcus pneumoniae by reverse vaccinology and genetic diversity of these proteins in clinical isolates.

作者信息

Argondizzo Ana Paula Corrêa, da Mota Fabio Faria, Pestana Cristiane Pinheiro, Reis Joice Neves, de Miranda Antonio Basílio, Galler Ricardo, Medeiros Marco Alberto

机构信息

Laboratory of Recombinant Technology, Bio-Manguinhos, Vice Diretoria de Desenvolvimento Tecnológico, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil,

出版信息

Appl Biochem Biotechnol. 2015 Feb;175(4):2124-65. doi: 10.1007/s12010-014-1375-3. Epub 2014 Dec 2.

DOI:10.1007/s12010-014-1375-3
PMID:25448632
Abstract

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Virulence-associated proteins common and conserved among all capsular types now represent the best strategy to combat pneumococcal infections. Our aim was to identify conserved targets in pneumococci that showed positive prediction for lipoprotein and extracellular subcellular location using bioinformatics programs and verify the distribution and the degree of conservation of these targets in pneumococci. These targets can be considered potential vaccine candidate to be evaluated in the future. A set of 13 targets were analyzed and confirmed the presence in all pneumococci tested. These 13 genes were highly conserved showing around >96 % of amino acid and nucleotide identity, but they were also present and show high identity in the closely related species Streptococcus mitis, Streptococcus oralis, and Streptococcus pseudopneumoniae. S. oralis clusters away from S. pneumoniae, while S. pseudopneumoniae and S. mitis cluster closer. The divergence between the selected targets was too small to be observed consistently in phylogenetic groups between the analyzed genomes of S. pneumoniae. The proteins analyzed fulfill two of the initial criteria of a vaccine candidate: targets are present in a variety of different pneumococci strains including different serotypes and are conserved among the samples evaluated.

摘要

肺炎链球菌是全球发病和死亡的主要原因。所有荚膜类型中常见且保守的与毒力相关的蛋白质,现在是对抗肺炎球菌感染的最佳策略。我们的目标是利用生物信息学程序在肺炎球菌中鉴定出对脂蛋白和细胞外亚细胞定位显示出阳性预测的保守靶点,并验证这些靶点在肺炎球菌中的分布和保守程度。这些靶点可被视为未来有待评估的潜在疫苗候选物。分析了一组13个靶点,并证实其存在于所有测试的肺炎球菌中。这13个基因高度保守,氨基酸和核苷酸同一性约>96%,但它们在密切相关的物种缓症链球菌、口腔链球菌和伪肺炎链球菌中也存在且显示出高度同一性。口腔链球菌与肺炎链球菌聚类较远,而伪肺炎链球菌和缓症链球菌聚类较近。所选靶点之间的差异太小,以至于在肺炎链球菌分析基因组的系统发育组中无法一致观察到。所分析的蛋白质满足疫苗候选物的两个初始标准:靶点存在于包括不同血清型在内的多种不同肺炎球菌菌株中,并且在所评估的样本中是保守的。

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