ArticleThe Journal of biological chemistry2014
Benzothiazinones mediate killing of Corynebacterineae by blocking decaprenyl phosphate recycling involved in cell wall biosynthesis.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Pardon the interruption: how Und-P sequestration has reshaped our understanding of the bacterial cell envelope.Journal of bacteriology · 2026Review
- The conserved σD envelope stress response monitors multiple aspects of envelope integrity in corynebacteria.PLoS genetics · 2024Article
- Top five unanswered questions in bacterial cell wall research.Cell surface (Amsterdam, Netherlands) · 2024Review
- Characterization of lipid composition and nutritional quality of yak ghee at different altitudes: A quantitative lipidomic analysis.Food chemistry: X · 2024Article
- Article
- Effects of benzothiazinone and ethambutol on the integrity of the corynebacterial cell envelope.Cell surface (Amsterdam, Netherlands) · 2023Article
- Profiling cell envelope-antibiotic interactions reveals vulnerabilities to β-lactams in a multidrug-resistant bacterium.Nature communications · 2023Article
- Molecular Mechanisms of MmpL3 Function and Inhibition.Microbial drug resistance (Larchmont, N.Y.) · 2023Review
- Repurposing the Pathogen Box compounds for identification of potent anti-malarials against blood stages of Plasmodium falciparum with PfUCHL3 inhibitory activity.Scientific reports · 2022Article
- Article
- Bacterial Cell Wall Modification with a Glycolipid Substrate.Journal of the American Chemical Society · 2019Article
- Metabolism Shapes the Cell.Journal of bacteriology · 2017Review
- Interrupting Biosynthesis of O Antigen or the Lipopolysaccharide Core Produces Morphological Defects in Escherichia coli by Sequestering Undecaprenyl Phosphate.Journal of bacteriology · 2016Article
- Impact of LytR-CpsA-Psr Proteins on Cell Wall Biosynthesis in Corynebacterium glutamicum.Journal of bacteriology · 2016Article
- Membrane remodelling in bacteria.Journal of structural biology · 2016Review
- Article
- Endless Resistance. Endless Antibiotics?MedChemComm · 2016Article
- CpsA, a LytR-CpsA-Psr Family Protein in Mycobacterium marinum, Is Required for Cell Wall Integrity and Virulence.Infection and immunity · 2015Article
- The Mycobacterial Cell Wall--Peptidoglycan and Arabinogalactan.Cold Spring Harbor perspectives in medicine · 2015Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Benzothiazinones (BTZs) are a new class of sulfur containing heterocyclic compounds that target DprE1, an oxidoreductase involved in the epimerization of decaprenyl-phosphoribose (DPR) to decaprenyl-phosphoarabinose (DPA) in the Corynebacterineae, such as Corynebacterium glutamicum and Mycobacterium tuberculosis. As a result, BTZ inhibition leads to inhibition of cell wall arabinan biosynthesis. Previous studies have demonstrated the essentiality of dprE1. In contrast, Cg-UbiA a ribosyltransferase, which catalyzes the first step of DPR biosynthesis prior to DprE1, when genetically disrupted, produced a viable mutant, suggesting that although BTZ biochemically targets DprE1, killing also occurs through chemical synthetic lethality, presumably through the lack of decaprenyl phosphate recycling. To test this hypothesis, a derivative of BTZ, BTZ043, was examined in detail against C. glutamicum and C. glutamicum::ubiA. The wild type strain was sensitive to BTZ043; however, C. glutamicum::ubiA was found to be resistant, despite possessing a functional DprE1. When the gene encoding C. glutamicum Z-decaprenyl-diphosphate synthase (NCgl2203) was overexpressed in wild type C. glutamicum, resistance to BTZ043 was further increased. This data demonstrates that in the presence of BTZ, the bacilli accumulate DPR and fail to recycle decaprenyl phosphate, which results in the depletion of decaprenyl phosphate and ultimately leads to cell death.
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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.