APM OpenIR
Deciphering molecular mechanism of silver by integrated omic approaches enables enhancing its antimicrobial efficacy in E. coli
Wang, Haibo1; Yan, Aixin2; Liu, Zhigang3; Yang, Xinming1; Xu, Zeling2; Wang, Yuchuan4; Wang, Runming1; Koohi-Moghadam, Mohamad1; Hu, Ligang5; Xia, Wei4; Tang, Huiru6,7; Wang, Yulan8; Li, Hongyan1; Sun, Hongzhe1
2019-06-01
Source PublicationPLOS BIOLOGY
ISSN1544-9173
Volume17Issue:6Pages:31
AbstractDespite the broad-spectrum antimicrobial activities of silver, its internal usage is restricted, owing to the toxicity. Strategies to enhance its efficacy are highly desirable but rely heavily on the understanding of its molecular mechanism of action. However, up to now, no direct silver-targeting proteins have been mined at a proteome-wide scale, which hinders systemic studies on the biological pathways interrupted by silver. Herein, we build up a unique system, namely liquid chromatography gel electrophoresis inductively coupled plasma mass spectrometry (LC-GE-ICP-MS), allowing 34 proteins directly bound by silver ions to be identified in Escherichia coli. By using integrated omic approaches, including metalloproteomics, metabolomics, bioinformatics, and systemic biology, we delineated the first dynamic antimicrobial actions of silver (Ag+) in E. coli, i.e., it primarily damages multiple enzymes in glycolysis and tricarboxylic acid (TCA) cycle, leading to the stalling of the oxidative branch of the TCA cycle and an adaptive metabolic divergence to the reductive glyoxylate pathway. It then further damages the adaptive glyoxylate pathway and suppresses the cellular oxidative stress responses, causing systemic damages and death of the bacterium. To harness these novel findings, we coadministrated metabolites involved in the Krebs cycles with Ag+ and found that they can significantly potentiate the efficacy of silver both in vitro and in an animal model. Our study reveals the comprehensive and dynamic mechanisms of Ag+ toxicity in E. coli cells and offers a novel and general approach for deciphering molecular mechanisms of metallodrugs in various pathogens and cells to facilitate the development of new therapeutics.
Funding OrganizationResearch Grants Council of Hong Kong ; Research Grants Council of Hong Kong ; National Science Foundation of China ; National Science Foundation of China ; University of Hong Kong ; University of Hong Kong ; Hong Kong PhD Fellowship (HKPF) ; Hong Kong PhD Fellowship (HKPF) ; Research Grants Council of Hong Kong ; Research Grants Council of Hong Kong ; National Science Foundation of China ; National Science Foundation of China ; University of Hong Kong ; University of Hong Kong ; Hong Kong PhD Fellowship (HKPF) ; Hong Kong PhD Fellowship (HKPF) ; Research Grants Council of Hong Kong ; Research Grants Council of Hong Kong ; National Science Foundation of China ; National Science Foundation of China ; University of Hong Kong ; University of Hong Kong ; Hong Kong PhD Fellowship (HKPF) ; Hong Kong PhD Fellowship (HKPF) ; Research Grants Council of Hong Kong ; Research Grants Council of Hong Kong ; National Science Foundation of China ; National Science Foundation of China ; University of Hong Kong ; University of Hong Kong ; Hong Kong PhD Fellowship (HKPF) ; Hong Kong PhD Fellowship (HKPF)
DOI10.1371/journal.pbio.3000292
WOS KeywordESCHERICHIA-COLI ; ANTIBACTERIAL ACTION ; GEL-ELECTROPHORESIS ; RESPIRATORY-CHAIN ; PROTEINS ; BINDING ; CELLS ; ION ; IDENTIFICATION ; NANOPARTICLES
Language英语
Funding ProjectResearch Grants Council of Hong Kong[17305415] ; Research Grants Council of Hong Kong[1733616] ; Research Grants Council of Hong Kong[17307017] ; National Science Foundation of China[21671203] ; University of Hong Kong ; Hong Kong PhD Fellowship (HKPF)
Funding OrganizationResearch Grants Council of Hong Kong ; Research Grants Council of Hong Kong ; National Science Foundation of China ; National Science Foundation of China ; University of Hong Kong ; University of Hong Kong ; Hong Kong PhD Fellowship (HKPF) ; Hong Kong PhD Fellowship (HKPF) ; Research Grants Council of Hong Kong ; Research Grants Council of Hong Kong ; National Science Foundation of China ; National Science Foundation of China ; University of Hong Kong ; University of Hong Kong ; Hong Kong PhD Fellowship (HKPF) ; Hong Kong PhD Fellowship (HKPF) ; Research Grants Council of Hong Kong ; Research Grants Council of Hong Kong ; National Science Foundation of China ; National Science Foundation of China ; University of Hong Kong ; University of Hong Kong ; Hong Kong PhD Fellowship (HKPF) ; Hong Kong PhD Fellowship (HKPF) ; Research Grants Council of Hong Kong ; Research Grants Council of Hong Kong ; National Science Foundation of China ; National Science Foundation of China ; University of Hong Kong ; University of Hong Kong ; Hong Kong PhD Fellowship (HKPF) ; Hong Kong PhD Fellowship (HKPF)
WOS Research AreaBiochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
WOS SubjectBiochemistry & Molecular Biology ; Biology
WOS IDWOS:000473675900017
PublisherPUBLIC LIBRARY SCIENCE
Citation statistics
Cited Times:9[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.apm.ac.cn/handle/112942/14631
Collection中国科学院武汉物理与数学研究所
Corresponding AuthorSun, Hongzhe
Affiliation1.Univ Hong Kong, Dept Chem, Hong Kong, Peoples R China
2.Univ Hong Kong, Sch Biol Sci, Hong Kong, Peoples R China
3.Chinese Acad Sci, Natl Ctr Magnet Resonance Wuhan, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan Inst Phys & Math,CAS Key Lab Magnet Resonan, Wuhan, Hubei, Peoples R China
4.Sun Yat Sen Univ, Sch Chem, Guangzhou, Guangdong, Peoples R China
5.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing, Peoples R China
6.Zhongshan Hosp, State Key Lab Genet Engn, Shanghai, Peoples R China
7.Fudan Univ, Sch Life Sci, Shanghai Int Ctr Mol Phen, Collaborat Innovat Ctr Genet & Dev, Shanghai, Peoples R China
8.Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore Phenome Ctr, Singapore, Singapore
Recommended Citation
GB/T 7714
Wang, Haibo,Yan, Aixin,Liu, Zhigang,et al. Deciphering molecular mechanism of silver by integrated omic approaches enables enhancing its antimicrobial efficacy in E. coli[J]. PLOS BIOLOGY,2019,17(6):31.
APA Wang, Haibo.,Yan, Aixin.,Liu, Zhigang.,Yang, Xinming.,Xu, Zeling.,...&Sun, Hongzhe.(2019).Deciphering molecular mechanism of silver by integrated omic approaches enables enhancing its antimicrobial efficacy in E. coli.PLOS BIOLOGY,17(6),31.
MLA Wang, Haibo,et al."Deciphering molecular mechanism of silver by integrated omic approaches enables enhancing its antimicrobial efficacy in E. coli".PLOS BIOLOGY 17.6(2019):31.
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