ArticlePLoS biology2018
Metallochaperone UreG serves as a new target for design of urease inhibitor: A novel strategy for development of antimicrobials.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 50 citations in OpenAlex.
- Article
- Urease inhibitors: current advances, therapeutic potentials, and clinical challenges.Future medicinal chemistry · 2026Review
- In Silico and In Vitro Elucidation of the Inhibitory Mechanism of Chlorogenic Acid AgainstFood science & nutrition · 2026Article
- The arsenic proteome in cancer: Unravelling molecular mechanisms of anticancer drugs.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026Review
- Urinary tract infections in diabetes: clinical significance and management approaches.Acta biochimica Polonica · 2026Review
- Unprecedented allosteric inhibition ofChemical science · 2025Article
- Role of UropathogenicPathogens (Basel, Switzerland) · 2025Review
- Prevalence of Helicobacter pylori infection in patients with upper gastrointestinal disorders using different methods in Khuzestan, Southwest Iran.Molecular biology reports · 2025Article
- Anti-urease therapy: a targeted approach to mitigating antibiotic resistance in Helicobacter pylori while preserving the gut microflora.Gut pathogens · 2025Review
- Metal-Based Approaches for the Fight against Antimicrobial Resistance: Mechanisms, Opportunities, and Challenges.Journal of the American Chemical Society · 2025Review
- New Directions inInfection and drug resistance · 2025Review
- Review
- Metal-detection based techniques and their applications in metallobiology.Chemical science · 2024Review
- Targeting bacterial nickel transport with aspergillomarasmine A suppresses virulence-associated Ni-dependent enzymes.Nature communications · 2024Article
- Epiberberine: a potential rumen microbial urease inhibitor to reduce ammonia release screened by targeting UreG.Applied microbiology and biotechnology · 2024Article
- Pyridylpiperazine-based carbodithioates as urease inhibitors: synthesis and biological evaluation.Frontiers in chemistry · 2024Article
- Article
- Delivering a toxic metal to the active site of urease.Science advances · 2023Article
- Mitochondrial ATP synthase as a direct molecular target of chromium(III) to ameliorate hyperglycaemia stress.Nature communications · 2023Article
- The role of nucleoside triphosphate hydrolase metallochaperones in making metalloenzymes.Metallomics : integrated biometal science · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Urease as a potential target of antimicrobial drugs has received considerable attention given its versatile roles in microbial infection. Development of effective urease inhibitors, however, is a significant challenge due to the deeply buried active site and highly specific substrate of a bacterial urease. Conventionally, urease inhibitors are designed by either targeting the active site or mimicking substrate of urease, which is not efficient. Up to now, only one effective inhibitor-acetohydroxamic acid (AHA)-is clinically available, but it has adverse side effects. Herein, we demonstrate that a clinically used drug, colloidal bismuth subcitrate, utilizes an unusual way to inhibit urease activity, i.e., disruption of urease maturation process via functional perturbation of a metallochaperone, UreG. Similar phenomena were also observed in various pathogenic bacteria, suggesting that UreG may serve as a general target for design of new types of urease inhibitors. Using Helicobacter pylori UreG as a showcase, by virtual screening combined with experimental validation, we show that two compounds targeting UreG also efficiently inhibited urease activity with inhibitory concentration (IC)50 values of micromolar level, resulting in attenuated virulence of the pathogen. We further demonstrate the efficacy of the compounds in a mammalian cell infection model. This study opens up a new opportunity for the design of more effective urease inhibitors and clearly indicates that metallochaperones involved in the maturation of important microbial metalloenzymes serve as new targets for devising a new type of antimicrobial drugs.
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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.