ArticleAntimicrobial agents and chemotherapy2006
Novel bacterial acetyl coenzyme A carboxylase inhibitors with antibiotic efficacy in vivo.
Article in Antimicrobial agents and chemotherapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 71 citations in OpenAlex.
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- Butuanimides, Fatty Acid Synthesis-Inhibiting Antibiotics from Symbiotic Bacteria.ACS chemical biology · 2026Article
- Species-Level Comparative Metagenomic Analysis of the Bacterial Abundance of the Gut Microbiome in Psoriasis, Hidradenitis Suppurativa, and Pemphigus Foliaceous Patients Using Shotgun Next-Generation Sequencing.International journal of molecular sciences · 2026Article
- Protein profile of the Escherichia coli strain, BW25113, exposed to two novel iron-halide compounds: Fe(Hampy)2Cl4 and Fe(Hampy)2Br4.Access microbiology · 2025Article
- Analysis of the Antibiotic-Potentiating Activity, Absorption, Distribution, Metabolism, and Excretion (ADME) and the Molecular Docking Properties of Phytol Against Multi-Drug-Resistant (MDR) Strains.Antibiotics (Basel, Switzerland) · 2024Article
- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
- Whole genome-scale assessment of gene fitness of Novosphingobium aromaticavorans during spaceflight.BMC genomics · 2023Article
- Lipid-Centric Approaches in Combating Infectious Diseases: Antibacterials, Antifungals and Antivirals with Lipid-Associated Mechanisms of Action.Antibiotics (Basel, Switzerland) · 2023Review
- Improved production of andrimid in Erwinia persicina BST187 strain by fermentation optimization.BMC microbiology · 2023Article
- Proteomic Profiling Reveals Cytotoxic Mechanisms of Action and Adaptive Mechanisms of Resistance inACS omega · 2023Article
- Heterobivalent Inhibitors of Acetyl-CoA Carboxylase: Drug Target Residence Time and Time-Dependent Antibacterial Activity.Journal of medicinal chemistry · 2022Article
- Article
- Bacterial fatty acid metabolism in modern antibiotic discovery.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Review
- An integrated computational-experimental approach reveals Yersinia pestis genes essential across a narrow or a broad range of environmental conditions.BMC microbiology · 2017Article
- Cell-free Determination of Binary Complexes That Comprise Extended Protein-Protein Interaction Networks of Yersinia pestis.Molecular & cellular proteomics : MCP · 2016Article
- Crystal Structure of Carboxyltransferase from Staphylococcus aureus Bound to the Antibacterial Agent Moiramide B.Biochemistry · 2016Article
- The essential genome of Streptococcus agalactiae.BMC genomics · 2016Article
- How bacterial pathogens eat host lipids: implications for the development of fatty acid synthesis therapeutics.The Journal of biological chemistry · 2015Review
- Scrutinizing the scaffolds of marine biosynthetics from different source organisms: Gram-negative cultured bacterial products enter center stage.Journal of natural products · 2014Review
- Identification and analysis of potential targets in Streptococcus sanguinis using computer aided protein data analysis.Advances and applications in bioinformatics and chemistry : AABC · 2014Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pseudopeptide pyrrolidinedione antibiotics, such as moiramide B, have recently been discovered to target the multisubunit acetyl coenzyme A (acetyl-CoA) carboxylases of bacteria. In this paper, we describe synthetic variations of each moiety of the modularly composed pyrrolidinediones, providing insight into structure-activity relationships of biochemical target activity, in vitro potency, and in vivo efficacy. The novel derivatives showed highly improved activities against gram-positive bacteria compared to those of previously reported variants. The compounds exhibited a MIC(90) value of 0.1 microg/ml against a broad spectrum of Staphylococcus aureus clinical isolates. No cross-resistance to antibiotics currently used in clinical practice was observed. Resistance mutations induced by pyrrolidinediones are exclusively located in the carboxyltransferase subunits of the bacterial acetyl-CoA carboxylase, indicating the identical mechanisms of action of all derivatives tested. Improvement of the physicochemical profile was achieved by salt formation, leading to aqueous solubilities of up to 5 g/liter. For the first time, the in vitro activity of this compound class was compared with its in vivo efficacy, demonstrating a path from compounds weakly active in vivo to agents with significant efficacy. In a murine model of S. aureus sepsis, the 100% effective dose of the best compound reported was 25 mg/kg of body weight, only fourfold higher than that of the comparator molecule linezolid. The obvious improvements achieved by chemical derivatization reflect the potential of this novel antibiotic compound class for future therapy.
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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.