University of Jeddah, Faculty of Science, Department of Biology, Jeddah, Saudi Arabia.
Braz J Biol. 2023 Feb 13;84:e269313. doi: 10.1590/1519-6984.269313. eCollection 2023.
The emergence of antibiotic resistance (AR) in bacteria is becoming an alarming health concern because it allows them to adapt themselves to changing environments. It is possible to prevent the spread of AR in many ways, such as reducing antibiotic misuse in human and veterinary medicine. Streptococcus pseudopneumoniae is one of these AR bacterial species that can cause pneumonia in humans and is responsible for high mortality and morbidity rates. It is oval shaped gram-positive bacterium that shows resistance to several antibiotics like penicillin, tetracycline, ciprofloxacin, erythromycin, and co-trimoxazale and no approved vaccine is available to overcome diseases of the pathogen. Thus, substantial efforts are necessary to select protective antigens from a whole genome of pathogens that are easily tested experimentally. The in silico designed vaccine was safe and potent in immunizing individuals against the aforementioned pathogens. Herein, we utilized a subtractive genomic approach to identify potential epitope-based vaccine candidates against S. pseudopneumoniae. In total, 50850 proteins were retrieved from the NCBI, representing the complete genome of S. pseudopneumoniae. Out of the total, CD-HIT analysis identified 1022 proteins as non-redundant and 49828 proteins as redundant and further subjected for subcellular localization in which bulk of proteins was located in the cytoplasm, with seven extracellular proteins (penicillin-binding protein, alpha-amylase, solute-binding protein, hypothetical protein, CHAP domain-containing protein, polysaccharide deacetylase family protein, hypothetical protein). Six immune cells epitopes (SNLQSENDRL, RNDSLQKQAR, NPTTTSEGF, KVKKKNNKK, AYSQGSQKEH, and SVVDQVSGDF) were predicted with the help of the IEDB server. To design a multi-epitopes vaccine these immune cell epitopes were together by GPGPG and adjuvant linker to enhance immune response efficacy. The 3D structure of the designed vaccine was modeled and conducted molecular docking and dynamic simulation studies were to check the binding efficacy with immune cells receptor and dynamic behavior of the docked complex. Finally, we concluded that the designed vaccine construct can provoke a proper and protective immune response against S. pseudopneumoniae.
细菌对抗生素耐药性（AR）的出现正成为一个令人担忧的健康问题，因为它使细菌能够适应不断变化的环境。可以通过多种方式预防 AR 的传播，例如减少人类和兽医医学中抗生素的滥用。肺炎链球菌是引起人类肺炎的 AR 细菌之一，其死亡率和发病率都很高。它是一种椭圆形革兰氏阳性细菌，对青霉素、四环素、环丙沙星、红霉素和复方新诺明等几种抗生素具有耐药性，目前还没有批准的疫苗来克服该病原体引起的疾病。因此，有必要从病原体的整个基因组中选择保护性抗原，这些抗原很容易通过实验进行测试。在此，我们利用消减基因组方法来鉴定针对肺炎链球菌的潜在基于表位的疫苗候选物。总共从 NCBI 检索了 50850 种蛋白质，代表肺炎链球菌的完整基因组。在总数中，CD-HIT 分析将 1022 种蛋白质鉴定为非冗余，49828 种蛋白质为冗余，并进一步进行亚细胞定位，其中大部分蛋白质位于细胞质中，有 7 种细胞外蛋白（青霉素结合蛋白、α-淀粉酶、溶质结合蛋白、假设蛋白、CHAP 结构域包含蛋白、多糖脱乙酰酶家族蛋白、假设蛋白）。借助 IEDB 服务器预测了 6 个免疫细胞表位（SNLQSENDRL、RNDSLQKQAR、NPTTTSEGF、KVKKKNNKK、AYSQGSQKEH 和 SVVDQVSGDF）。为了设计一种多表位疫苗，我们使用 GPGPG 和佐剂接头将这些免疫细胞表位一起连接起来，以增强免疫反应的效果。设计的疫苗的 3D 结构进行建模，并进行分子对接和动态模拟研究，以检查与免疫细胞受体的结合效果和对接复合物的动态行为。最后，我们得出结论，设计的疫苗构建体可以引发针对肺炎链球菌的适当和保护性免疫反应。
