ArticleAntimicrobial agents and chemotherapy2015
A novel antimycobacterial compound acts as an intracellular iron chelator.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 40 citations in OpenAlex.
- Iron-Reversible Bactericidal Activity of Marine-DerivedMarine drugs · 2026Article
- Mutations in the Esx-3 secretion system confer resistance to multiple chemical scaffolds inMicrobiology (Reading, England) · 2025Article
- Genome-wide phenotypic insights into mycobacterial virulence using Drosophila melanogaster.PLoS pathogens · 2025Article
- VLX600, an anticancer iron chelator, exerts antimicrobial effects onMicrobiology spectrum · 2025Article
- Mycobacterium susceptibility to ivermectin by inhibition of eccD3, an ESX-3 secretion system component.PLoS computational biology · 2025Article
- Mycobactin and clofazimine activity are negatively correlated in mycobacteria.Frontiers in microbiology · 2025Article
- TargetingRSC medicinal chemistry · 2023Review
- Differentiating the roles of Mycobacterium tuberculosis substrate binding proteins, FecB and FecB2, in iron uptake.PLoS pathogens · 2023Article
- The implication of Mycobacterium tuberculosis-mediated metabolism of targeted xenobiotics.Nature reviews. Chemistry · 2023Review
- Extracellular vesicles, a novel model linking bacteria to ferroptosis in the future?Applied microbiology and biotechnology · 2022Review
- Structure-Activity Relationships of Pyrazolo[1,5-ACS infectious diseases · 2021Article
- Antitubercular 2-Pyrazolylpyrimidinones: Structure-Activity Relationship and Mode-of-Action Studies.Journal of medicinal chemistry · 2021Article
- Iron Pathways and Iron Chelation Approaches in Viral, Microbial, and Fungal Infections.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Looking beyond Typical Treatments for Atypical Mycobacteria.Antibiotics (Basel, Switzerland) · 2020Review
- Genome-wide Phenotypic Profiling Identifies and Categorizes Genes Required for Mycobacterial Low Iron Fitness.Scientific reports · 2019Article
- Article
- Pyrazolopyrimidinones, a novel class of copper-dependent bactericidal antibiotics against multi-drug resistant S. aureus.Metallomics : integrated biometal science · 2019Article
- Bacterial Resistance in Pneumonia in Developing Countries-A Role for Iron Chelation.Tropical medicine and infectious disease · 2019Review
- Understanding lipidomic basis of iron limitation induced chemosensitization of drug-resistant3 Biotech · 2019Article
- A major role for ferroptosis inThe Journal of experimental medicine · 2019Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Efficient iron acquisition is crucial for the pathogenesis of Mycobacterium tuberculosis. Mycobacterial iron uptake and metabolism are therefore attractive targets for antitubercular drug development. Resistance mutations against a novel pyrazolopyrimidinone compound (PZP) that is active against M. tuberculosis have been identified within the gene cluster encoding the ESX-3 type VII secretion system. ESX-3 is required for mycobacterial iron acquisition through the mycobactin siderophore pathway, which could indicate that PZP restricts mycobacterial growth by targeting ESX-3 and thus iron uptake. Surprisingly, we show that ESX-3 is not the cellular target of the compound. We demonstrate that PZP indeed targets iron metabolism; however, we found that instead of inhibiting uptake of iron, PZP acts as an iron chelator, and we present evidence that the compound restricts mycobacterial growth by chelating intrabacterial iron. Thus, we have unraveled the unexpected mechanism of a novel antimycobacterial compound.
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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.