Fereshteh Sepideh, Noori Goodarzi Narjes, Sepehr Amin, Shafiei Morvarid, Ajdary Soheila, Badmasti Farzad
Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran.
Department of Pathobiology, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2022 May 9;21(1):e126559. doi: 10.5812/ijpr-126559. eCollection 2022 Dec.
is an important nosocomial pathogen causing high morbidity and mortality in immunocompromised patients with prolonged hospitalization. Multidrug-resistant infections are on the rise worldwide. Therefore, the discovery of an effective vaccine against this bacterium seems necessary as a cost-effective and preventive strategy.
In this present study, 35 genomes of strains were considered, and the extracellular proteins were selected, maximally having one transmembrane helix with high adhesion probability and no similarity to host proteins, as immunogenic candidates using the web tool Vaxign. Subsequently, the role of these selected proteins in bacterial pathogenesis was investigated using VICMpred. Then, the major histocompatibility complex class II, linear B-cell epitopes, and conservation of epitopes were identified using the Immune Epitope Database, BepiPred, and Epitope Conservancy Analysis, respectively. Finally, the B-cell discontinuous epitopes of each protein were predicted using ElliPro and plotted on the three-dimensional structure (3D) of the proteins. The role of the unknown proteins was predicted using the STRING database.
In this study, eight acceptable immunogenic candidates, including FilF, FimA, putative acid phosphatase, putative exported protein, subtilisin-like serine protease, and three uncharacterized proteins, were identified in .
The results of the STRING database showed that these three uncharacterized proteins play a role in nutrition (heme utilization), peptide bond cleavage (serine peptidases), and cellular processes (MlaD protein). Extracellular proteins might play a catalyst role in the outer membrane protein-based vaccine of . Furthermore, this study proposed a list of potent immunogenic candidates of extracellular proteins.
是一种重要的医院病原体,在长期住院的免疫功能低下患者中可导致高发病率和死亡率。耐多药感染在全球范围内呈上升趋势。因此,作为一种具有成本效益的预防策略,研发一种针对这种细菌的有效疫苗似乎很有必要。
在本研究中,考虑了35个菌株的基因组,并使用网络工具Vaxign选择细胞外蛋白作为免疫原性候选物,这些蛋白最多有一个跨膜螺旋,具有高粘附概率且与宿主蛋白无相似性。随后,使用VICMpred研究这些选定蛋白在细菌发病机制中的作用。然后,分别使用免疫表位数据库、BepiPred和表位保守性分析来鉴定主要组织相容性复合体II类、线性B细胞表位和表位的保守性。最后,使用ElliPro预测每种蛋白的B细胞不连续表位,并绘制在蛋白的三维结构上。使用STRING数据库预测未知蛋白的作用。
在本研究中,在中鉴定出8个可接受的免疫原性候选物,包括FilF、FimA、假定的酸性磷酸酶、假定的输出蛋白、枯草杆菌蛋白酶样丝氨酸蛋白酶和3个未鉴定的蛋白。
STRING数据库的结果表明,这3个未鉴定的蛋白在营养(血红素利用)、肽键裂解(丝氨酸蛋白酶)和细胞过程(MlaD蛋白)中发挥作用。细胞外蛋白可能在基于外膜蛋白的疫苗中起催化作用。此外,本研究提出了一份细胞外蛋白的有效免疫原性候选物清单。