ArticlePLoS biology2019
Deciphering molecular mechanism of silver by integrated omic approaches enables enhancing its antimicrobial efficacy in E. coli.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 104 citations in OpenAlex.
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- Microbial response and resistance mechanisms against diverse anthropogenic pollutants.Frontiers in microbiology · 2026Review
- Unprecedented allosteric inhibition ofChemical science · 2025Article
- Metal-Based Approaches for the Fight against Antimicrobial Resistance: Mechanisms, Opportunities, and Challenges.Journal of the American Chemical Society · 2025Review
- Modulation of the mechanism of action of antibacterial silver N-heterocyclic carbene complexes by variation of the halide ligand.RSC advances · 2025Article
- Intratracheal Instillation of Silver Nanoparticles to Rats Induces Mitochondrial Fission and Aortic Damage: Protective Effect of Sodium Selenite.International journal of nanomedicine · 2025Article
- Antimicrobial Activity and Mode of Action of N-Heterocyclic Carbene Silver(I) Complexes.Molecules (Basel, Switzerland) · 2024Article
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- Green synthesized silver nanoparticles, a sustainable approach for fruit and vegetable preservation: An overview.Food chemistry: X · 2024Review
- Antioxidant-related enzymes and peptides as biomarkers of metallic nanoparticles (eco)toxicity in the aquatic environment.Chemosphere · 2024Review
- Metal-detection based techniques and their applications in metallobiology.Chemical science · 2024Review
- The good, the bad, and the ugly of metals as antimicrobials.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Review
- Recent Advances in Metalloproteomics.Biomolecules · 2024Review
- The Substantial Role of Cell and Nanoparticle Surface Properties in the Antibacterial Potential of Spherical Silver Nanoparticles.Nanotechnology, science and applications · 2024Article
- Molecular mechanisms of tigecycline-resistance amongFrontiers in cellular and infection microbiology · 2024Review
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- Mitochondrial Oxidative Stress Is the General Reason for Apoptosis Induced by Different-Valence Heavy Metals in Cells and Mitochondria.International journal of molecular sciences · 2023Review
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- Insights into the Synergistic Antibacterial Activity of Silver Nitrate with Potassium Tellurite againstMicrobiology spectrum · 2023Article
- The Lung Microbiome in COPD and Lung Cancer: Exploring the Potential of Metal-Based Drugs.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite 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.
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Registered trials
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