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Eupomatenoid-5诱导后结核分枝杆菌的蛋白质组学图谱揭示了潜在的药物靶点。

Proteomic profile of Mycobacterium tuberculosis after eupomatenoid-5 induction reveals potential drug targets.

作者信息

Ghiraldi-Lopes Luciana D, Campanerut-Sá Paula Az, Meneguello Jean E, Seixas Flávio Av, Lopes-Ortiz Mariana A, Scodro Regiane Bl, Pires Claudia Ta, da Silva Rosi Z, Siqueira Vera Ld, Nakamura Celso V, Cardoso Rosilene F

机构信息

Postgraduate Program in Health Sciences, Department of Clinical Analyses & Biomedicine, State University of Maringá, Avenida Colombo, 5790, 87020-900, Maringá, Paraná, Brazil.

Department of Clinical Analyses & Biomedicine, State University of Maringá, Avenida Colombo, 5790, 87020-900, Maringá, Paraná, Brazil.

出版信息

Future Microbiol. 2017 Aug;12:867-879. doi: 10.2217/fmb-2017-0023. Epub 2017 Jul 7.

Abstract

AIM

We investigated a proteome profile, protein-protein interaction and morphological changes of Mycobacterium tuberculosis after different times of eupomatenoid-5 (EUP-5) induction to evaluate the cellular response to the drug-induced damages.

METHODS

The bacillus was induced to sub-minimal inhibitory concentration of EUP-5 at 12 h, 24 h and 48 h. The proteins were separated by 2D gel electrophoresis, identified by LC/MS-MS. Scanning electron microscopy and Search Tool for the Retrieval of Interacting Genes/Proteins analyses were performed.

RESULTS

EUP-5 impacts mainly in M. tuberculosis proteins of intermediary metabolism and interactome suggests a multisite disturbance that contributes to bacilli death. Scanning electron microscopy revealed the loss of bacillary form.

CONCLUSION

Some of the differentially expressed proteins have the potential to be drug targets such as citrate synthase (Rv0896), phosphoglycerate kinase (Rv1437), ketol-acid reductoisomerase (Rv3001c) and ATP synthase alpha chain (Rv1308).

摘要

目的

我们研究了在不同时间的优波马酮 - 5(EUP - 5)诱导后结核分枝杆菌的蛋白质组概况、蛋白质 - 蛋白质相互作用及形态变化,以评估细胞对药物诱导损伤的反应。

方法

在12小时、24小时和48小时将该杆菌诱导至低于最低抑菌浓度的EUP - 5。蛋白质通过二维凝胶电泳分离,经液相色谱/串联质谱鉴定。进行了扫描电子显微镜检查和用于检索相互作用基因/蛋白质的搜索工具分析。

结果

EUP - 5主要影响结核分枝杆菌中间代谢的蛋白质,相互作用组提示多位点干扰,这导致杆菌死亡。扫描电子显微镜显示杆菌形态丧失。

结论

一些差异表达的蛋白质有潜力成为药物靶点,如柠檬酸合酶(Rv0896)、磷酸甘油酸激酶(Rv1437)、酮醇酸还原异构酶(Rv3001c)和ATP合酶α链(Rv1308)。

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