淋病是一种紧迫的抗生素耐药性威胁,其治疗选择不断受到限制。此外,到目前为止,还没有批准针对它的疫苗。因此,本研究旨在针对耐抗生素淋病奈瑟菌菌株引入新的免疫原性和药物靶标。第一步,检索到了淋病奈瑟菌79个完整基因组的核心蛋白。接下来,表面暴露的蛋白质从不同方面进行评估,如抗原性,变应原性,水利,和B细胞和T细胞表位以引入有希望的免疫原性候选物。然后,与人Toll样受体(TLR-1、2和4)的相互作用,并模拟了引起体液和细胞免疫反应的免疫反应性。另一方面,为了识别新的广谱药物靶标,检测细胞质和必需蛋白。然后,将淋病奈瑟菌代谢组特异性蛋白与药物库的药物靶标进行了比较,并检索了新的药物靶标。最后,我们评估了蛋白质数据库(PDB)文件的可用性和ESKAPE组和常见性传播感染(STI)药物的患病率.我们的分析导致识别十个新的和推定的免疫原性靶标,包括murein转糖基酶A,PBP1A,奥帕,NlpD,Azurin,MtrE,RMPM,LptD,NspA,还有Tama.此外,确定了四个潜在的广谱药物靶标,包括UMP激酶,GlyQ,HU家族DNA结合蛋白,IF-1一些入围的免疫原性和药物靶标已确认在粘附中的作用,免疫逃避,和能诱导杀菌抗体的抗生素抗性。其他免疫原性和药物靶标也可能与淋病奈瑟菌的毒力有关。因此,建议进一步的实验研究和定点突变,以研究潜在的疫苗和药物靶点在淋病奈瑟菌发病机制中的作用.看来,提出新型疫苗和药物靶标的努力似乎为针对这种细菌的预防治疗策略铺平了道路。此外,杀菌单克隆抗体和抗生素的组合是治愈淋病奈瑟菌的一种有前途的方法。
Gonorrhea is an urgent antimicrobial resistance threat and its therapeutic options are continuously getting restricted. Moreover, no vaccine has been approved against it so far. Hence, the present study aimed to introduce novel immunogenic and drug targets against antibiotic-resistant Neisseria gonorrhoeae strains. In the first step, the core proteins of 79 complete genomes of N. gonorrhoeae were retrieved. Next, the surface-exposed proteins were evaluated from different aspects such as antigenicity, allergenicity, conservancy, and B-cell and T-cell epitopes to introduce promising immunogenic candidates. Then, the interactions with human Toll-like receptors (TLR-1, 2, and 4), and immunoreactivity to elicit humoral and cellular immune responses were simulated. On the other hand, to identify novel broad-spectrum drug targets, the cytoplasmic and essential proteins were detected. Then, the N. gonorrhoeae metabolome-specific proteins were compared to the drug targets of the DrugBank, and novel drug targets were retrieved. Finally, the protein data bank (PDB) file availability and prevalence among the ESKAPE group and common sexually transmitted infection (STI) agents were assessed. Our analyses resulted in the recognition of ten novel and putative immunogenic targets including murein transglycosylase A, PBP1A, Opa, NlpD, Azurin, MtrE, RmpM, LptD, NspA, and TamA. Moreover, four potential and broad-spectrum drug targets were identified including UMP kinase, GlyQ, HU family DNA-binding protein, and IF-1. Some of the shortlisted immunogenic and drug targets have confirmed roles in adhesion, immune evasion, and antibiotic resistance that can induce bactericidal antibodies. Other immunogenic and drug targets might be associated with the virulence of N. gonorrhoeae as well. Thus, further experimental studies and site-directed mutations are recommended to investigate the role of potential vaccine and drug targets in the pathogenesis of N. gonorrhoeae. It seems that the efforts for proposing novel vaccines and drug targets appear to be paving the way for a prevention-treatment strategy against this bacterium. Additionally, a combination of bactericidal monoclonal antibodies and antibiotics is a promising approach to curing N. gonorrhoeae.