Computer-aided genomic data analysis of drug-resistant Neisseria gonorrhoeae for the Identification of alternative therapeutic targets.
Computer-aided genomic data analysis of drug-resistant Neisseria gonorrhoeae for the Identification of alternative therapeutic targets.
复制标题
DOI：
10.3389/fcimb.2023.1017315
复制
发表时间：
2023
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
淋病奈瑟菌是一种新出现的多重耐药病原体，可在男性和女性中引起性传播感染。淋病奈瑟菌已显示出对已报道的抗生素的耐药性，因此引起了研究人员的注意，以解决这一问题。本研究旨在应用生物信息学方法寻找抗淋病奈瑟菌感染的新型药物和疫苗靶点。对69株淋病奈瑟菌进行全基因组测序，获得核心基因集。鉴定了淋病奈瑟菌必需和非同源代谢途径蛋白。此外，利用不同的生物信息学数据库进行下游分析。DrugBank数据库扫描在优先列表中确定了12个新的药物靶点。它们是对抗这种细菌的首选药物靶点。到目前为止，还没有针对淋病奈瑟菌感染的有效疫苗。在目前的研究中，两种外膜蛋白通过反向疫苗学方法优先作为候选疫苗。利用顶部的导联B细胞和t细胞重叠的表位来产生结合免疫调节佐剂、连接物和PADRE序列的嵌合疫苗结构。通过分子对接和MD模拟分析推断，排名最高的优先疫苗构建体（V7）与人类免疫细胞受体表现出稳定的分子相互作用。计算机免疫研究解释了免疫细胞的相当大的反应。需要额外的试探性验证，以确保针对淋病奈瑟菌感染的优先疫苗结构的有效性。所鉴定的蛋白可用于进一步合理的药物和疫苗设计，以开发潜在的治疗实体，以对抗多重耐药淋病奈瑟菌。
Neisseria gonorrhoeae is an emerging multidrug resistance pathogen that causes sexually transmitted infections in men and women. The N. gonorrhoeae has demonstrated an emerging antimicrobial resistance against reported antibiotics, hence fetching the attention of researchers to address this problem. The present in-silico study aimed to find putative novel drug and vaccine targets against N. gonorrhoeae infection by the application of bioinformatics approaches. Core genes set of 69 N. gonorrhoeae strains was acquired from complete genome sequences. The essential and non-homologous metabolic pathway proteins of N. gonorrhoeae were identified. Moreover, different bioinformatics databases were used for the downstream analysis. The DrugBank database scanning identified 12 novel drug targets in the prioritized list. They were preferred as drug targets against this bacterium. A viable vaccine is unavailable so far against N. gonorrhoeae infection. In the current study, two outer-membrane proteins were prioritized as vaccine candidates via reverse vaccinology approach. The top lead B and T-cells overlapped epitopes were utilized to generate a chimeric vaccine construct combined with immune-modulating adjuvants, linkers, and PADRE sequences. The top ranked prioritized vaccine construct (V7) showed stable molecular interaction with human immune cell receptors as inferred during the molecular docking and MD simulation analyses. Considerable response for immune cells was interpreted by in-silico immune studies. Additional tentative validation is required to ensure the effectiveness of the prioritized vaccine construct against N. gonorrhoeae infection. The identified proteins can be used for further rational drug and vaccine designing to develop potential therapeutic entities against the multi-drug resistant N. gonorrhoeae.