ArticleThe Journal of biological chemistry2012
Exometabolome analysis identifies pyruvate dehydrogenase as a target for the antibiotic triphenylbismuthdichloride in multiresistant bacterial pathogens.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 60 citations in OpenAlex.
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- Antibiotic Biosynthesis Pathways from EndophyticAntibiotics (Basel, Switzerland) · 2021Article
- Technologies for High-Throughput Identification of Antibiotic Mechanism of Action.Antibiotics (Basel, Switzerland) · 2021Review
- Exometabolomic Analysis of Decidualizing Human Endometrial Stromal and Perivascular Cells.Frontiers in cell and developmental biology · 2021Article
- Exogenous Citrulline and Glutamine Contribute to Reverse the Resistance ofFrontiers in microbiology · 2021Article
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- Host metabolites stimulate the bacterial proton motive force to enhance the activity of aminoglycoside antibiotics.PLoS pathogens · 2019Article
- A plant pathogenic bacterium exploits the tricarboxylic acid cycle metabolic pathway of its insect vector.Virulence · 2018Article
- The Potential of Systems Biology to Discover Antibacterial Mechanisms of Plant Phenolics.Frontiers in microbiology · 2017Review
- The omic approach to parasitic trematode research-a review of techniques and developments within the past 5 years.Parasitology research · 2016Review
- Untargeted Metabolomics To Ascertain Antibiotic Modes of Action.Antimicrobial agents and chemotherapy · 2016Article
- Application of Omics Technologies for Evaluation of Antibacterial Mechanisms of Action of Plant-Derived Products.Frontiers in microbiology · 2016Review
- Simultaneous Host-Pathogen Transcriptome Analysis during Granulibacter bethesdensis Infection of Neutrophils from Healthy Subjects and Patients with Chronic Granulomatous Disease.Infection and immunity · 2015Article
- Glycolytic dependency of high-level nitric oxide resistance and virulence in Staphylococcus aureus.mBio · 2015Article
- The utility of metabolomics in natural product and biomarker characterization.Biochimica et biophysica acta · 2014Review
- Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets.Diabetes · 2014Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The desperate need for new therapeutics against notoriously antibiotic-resistant bacteria has led to a quest for novel antibacterial target structures and compounds. Moreover, defining targets and modes of action of new antimicrobial compounds remains a major challenge with standard technologies. Here we characterize the antibacterial properties of triphenylbismuthdichloride (TPBC), which has recently been successfully used against device-associated infections. We demonstrate that TPBC has potent antimicrobial activity against many bacterial pathogens. Using an exometabolome profiling approach, a unique TPBC-mediated change in the metabolites of Staphylococcus aureus was identified, indicating that TPBC blocks bacterial pyruvate catabolism. Enzymatic studies showed that TPBC is a highly efficient, uncompetitive inhibitor of the bacterial pyruvate dehydrogenase complex. Our study demonstrates that metabolomics approaches can offer new avenues for studying the modes of action of antimicrobial compounds, and it indicates that inhibition of the bacterial pyruvate dehydrogenase complex may represent a promising strategy for combating multidrug-resistant bacteria.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.