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结核分支杆菌糖蛋白的一个有效亚类,作为疫苗和治疗靶点的相关候选物。

A potent subset of Mycobacterium tuberculosis glycoproteins as relevant candidates for vaccine and therapeutic target.

机构信息

TB Protein Chemistry Lab, Tuberculosis and Pulmonary Research Department, Pasteur Institute of Iran, Pasteur Ave, Tehran, 13164, Iran.

Hepatitis Research Center, Shahid Rahimi Hospital, Aligoudarz School of Nursing, Lorestan University of Medical Science, Khorramabad, Iran.

出版信息

Sci Rep. 2023 Dec 14;13(1):22194. doi: 10.1038/s41598-023-49665-2.

Abstract

Tuberculosis (TB) remains one of the most afflictive bacterial infections globally. In high burden TB countries, surveillance, diagnosis and treatment of drug resistant TB (RR and X/MDRTB) display a crucial public health challenge. Therefore, we need new TB vaccines; diagnostic and therapeutic strategies to briskly prevent disease promotion; reduce drug-resistant TB and protect everyone from disease. The study identified various potent membrane and cell wall M. tuberculosis glycolipoproteins that are relevant for diagnostics, drug and vaccine discovery. A M. tuberculosis Proskauer and Beck broth culture was extracted for total proteins by ammonium sulfate method. After ConA-Affinity Chromatography reputed glycoproteins were collected followed by 2DE gel electrophoresis and LC Mass spectrometry. A total of 293 glycoproteins were identified using GlycoPP and IEDB database. Probable conserved trans-membrane protein (Rv0954), LpqN (Rv0583), PPE68 (Rv3873), Phosphate-binding protein (Rv0932c), PPE61 (Rv3532) and LprA (Rv1270c), had the highest glycosylation percentage value with 13.86%, 11.84%, 11.68%, 11.1%, 10.59% and10.2%, respectively. Our study discloses several dominant glycoproteins that play roles in M. tuberculosis survival, and immunogenicity. These include glycoproteins involved in antigenicity, transport and biosynthesis of M. tuberculosis cell envelope, pathogen-host interaction and drug efflux pumps, which are considered as a feasible drug targets or TB new vaccine candidates.

摘要

结核病(TB)仍然是全球最具侵袭性的细菌感染之一。在高负担结核病国家,对耐药结核病(RR 和 X/MDRTB)的监测、诊断和治疗是一个关键的公共卫生挑战。因此,我们需要新的结核病疫苗;诊断和治疗策略,以迅速预防疾病的发展;减少耐药结核病,保护每个人免受疾病的侵害。该研究确定了各种潜在的结核分枝杆菌膜和细胞壁糖脂,这些糖脂与诊断、药物和疫苗发现有关。用硫酸铵法从结核分枝杆菌普罗克瑟和贝克肉汤培养物中提取总蛋白。经 ConA-亲和层析后,收集代表性糖蛋白,然后进行 2DE 凝胶电泳和 LC 质谱分析。使用 GlycoPP 和 IEDB 数据库共鉴定了 293 种糖蛋白。可能保守的跨膜蛋白(Rv0954)、LpqN(Rv0583)、PPE68(Rv3873)、磷酸盐结合蛋白(Rv0932c)、PPE61(Rv3532)和 LprA(Rv1270c)具有最高的糖基化百分比值,分别为 13.86%、11.84%、11.68%、11.1%、10.59%和 10.2%。我们的研究揭示了几种在结核分枝杆菌生存和免疫原性中起作用的主要糖蛋白。这些糖蛋白包括参与结核分枝杆菌细胞包膜的抗原性、运输和生物合成、病原体-宿主相互作用和药物外排泵的糖蛋白,它们被认为是可行的药物靶点或结核病的新疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5312/10719292/16d2de0074c9/41598_2023_49665_Fig1_HTML.jpg

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