ArticleThe Journal of biological chemistry2016
Activation of Exogenous Fatty Acids to Acyl-Acyl Carrier Protein Cannot Bypass FabI Inhibition in Neisseria.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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
23 citing papers in PubMed.
- Cloning, Expression, Purification and Biological Activity Analysis of Recombinant Helicobacter pylori FabI as a Drug Target.Molecular biotechnology · 2026Article
- The bactericidal FabI inhibitor Debio 1453 clears antibiotic-resistant Neisseria gonorrhoeae infection in vivo.Nature communications · 2025Article
- Vibrio cholerae can Recycle Fatty Acids Via an Acyl-Acyl Carrier Protein Synthetase.Current microbiology · 2025Article
- Structure and catalytic mechanism of exogenous fatty acid recycling by AasS, a versatile acyl-ACP synthetase.Nature structural & molecular biology · 2025Article
- Bacterial acquisition of host fatty acids has far-reaching implications on virulence.Microbiology and molecular biology reviews : MMBR · 2024Review
- An inhibitory mechanism of AasS, an exogenous fatty acid scavenger: Implications for re-sensitization of FAS II antimicrobials.PLoS pathogens · 2024Article
- A broad inhibitor of acyl-acyl carrier protein synthetases.Biochemistry and biophysics reports · 2023Article
- Incorporation, fate, and turnover of free fatty acids in cyanobacteria.FEMS microbiology reviews · 2023Review
- CanB is a metabolic mediator of antibiotic resistance in Neisseria gonorrhoeae.Nature microbiology · 2023Article
- Structure and mechanism for streptococcal fatty acid kinase (Fak) system dedicated to host fatty acid scavenging.Science advances · 2022Article
- Specialized acyl carrier protein used by serine palmitoyltransferase to synthesize sphingolipids inFrontiers in microbiology · 2022Article
- Synthesis of an acyl-acyl carrier protein synthetase inhibitor to study fatty acid recycling.Scientific reports · 2020Article
- Structural approaches to pathway-specific antimicrobial agents.Translational research : the journal of laboratory and clinical medicine · 2020Review
- The genome of a Bacteroidetes inhabitant of the human gut encodes a structurally distinct enoyl-acyl carrier protein reductase (FabI).The Journal of biological chemistry · 2020Article
- Article
- Fatty acid activation and utilization by Alistipes finegoldii, a representative Bacteroidetes resident of the human gut microbiome.Molecular microbiology · 2020Article
- Article
- Therapeutic Targets in Chlamydial Fatty Acid and Phospholipid Synthesis.Frontiers in microbiology · 2018Review
- Bacterial fatty acid metabolism in modern antibiotic discovery.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Review
- Exogenous fatty acid metabolism in bacteria.Biochimie · 2017Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Neisseria is a Gram-negative pathogen with phospholipids composed of straight chain saturated and monounsaturated fatty acids, the ability to incorporate exogenous fatty acids, and lipopolysaccharides that are not essential. The FabI inhibitor, AFN-1252, was deployed as a chemical biology tool to determine whether Neisseria can bypass the inhibition of fatty acid synthesis by incorporating exogenous fatty acids. Neisseria encodes a functional FabI that was potently inhibited by AFN-1252. AFN-1252 caused a dose-dependent inhibition of fatty acid synthesis in growing Neisseria, a delayed inhibition of growth phenotype, and minimal inhibition of DNA, RNA, and protein synthesis, showing that its mode of action is through inhibiting fatty acid synthesis. Isotopic fatty acid labeling experiments showed that Neisseria encodes the ability to incorporate exogenous fatty acids into its phospholipids by an acyl-acyl carrier protein-dependent pathway. However, AFN-1252 remained an effective antibacterial when Neisseria were supplemented with exogenous fatty acids. These results demonstrate that extracellular fatty acids are activated by an acyl-acyl carrier protein synthetase (AasN) and validate type II fatty acid synthesis (FabI) as a therapeutic target against Neisseria.
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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.