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Identification Of Anti-gram-negative Bacteria Agents Targeting The Interaction Between Ribosomal Proteins L12 And L10

Title: Identification Of Anti-gram-negative Bacteria Agents Targeting The Interaction Between Ribosomal Proteins L12 And L10.
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Name(s): Wang, Weiwei, author
Liu, Chao, author
Zhu, Ningyu, author
Lin, Yuan, author
Jiang, Jiandong, author
Wang, Yanchang, author
Li, Yan, author
Si, Shuyi, author
Type of Resource: text
Genre: Journal Article
Text
Journal Article
Date Issued: 2018-09-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Gram-negative bacteria have become the main pathogens and cause serious clinical problems with increased morbidity and mortality. However, the slow discovery of new antimicrobial agents is unable to meet the need for the treatment of bacterial infections caused by drug-resistant strains. The interaction of L12 and L10 is essential for ribosomal function and protein synthesis. In this study, a yeast two-hybrid system was established to successfully detect the interaction between L12 and L10 proteins from gram-negative bacteria Escherichia coli, which allows us to screen compounds that specifically disrupt this interaction. With this system, we identified two compounds IMB-84 and IMB-87 that block L12-L10 interaction and show bactericidal activity against E. coli. We used glutathione-S-transferase (GST) pull-down and surface plasmon resonance (SPR) assays to demonstrate that these compounds disrupt L12-L10 interaction in vitro and the target of compounds was further confirmed by the overexpression of target proteins. Moreover, protein synthesis and elongation factor G-dependent GTPase activities are inhibited by two compounds. Therefore, we have identified two antibacterial agents that disrupt L12-L10 interaction by using yeast two-hybrid system. (C) 2018 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
Identifier: FSU_libsubv1_wos_000445032400007 (IID), 10.1016/j.apsb.2018.07.006 (DOI)
Keywords: binding, discovery, region, rna, emergence, antibiotic-resistance, Antimicrobial agents, elongation-factor-g, Escherichia coll, l12/l10, l7/12, Ribosome, site, yeast 2-hybrid system, Yeast two-hybrid
Publication Note: The publisher’s version of record is available at https://doi.org/10.1016/j.apsb.2018.07.006
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000445032400007
Owner Institution: FSU
Is Part Of: Acta Pharmaceutica Sinica B.
2211-3835
Issue: iss. 5, vol. 8

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Wang, W., Liu, C., Zhu, N., Lin, Y., Jiang, J., Wang, Y., … Si, S. (2018). Identification Of Anti-gram-negative Bacteria Agents Targeting The Interaction Between Ribosomal Proteins L12 And L10. Acta Pharmaceutica Sinica B. Retrieved from http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000445032400007