ArticleAntimicrobial agents and chemotherapy2013
Perturbation of Staphylococcus aureus gene expression by the enoyl-acyl carrier protein reductase inhibitor AFN-1252.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 32 citations in OpenAlex.
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- Treatment ofAntimicrobial agents and chemotherapy · 2025Article
- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
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- Antibiotics in the clinical pipeline in October 2019.The Journal of antibiotics · 2020Review
- Small-Molecule Inhibition of theACS chemical biology · 2019Article
- Virulence Factor Targeting of the Bacterial Pathogen Staphylococcus aureus for Vaccine and Therapeutics.Current drug targets · 2018Review
- Bacterial fatty acid metabolism in modern antibiotic discovery.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Review
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- Pharmacological Targeting of the Host-Pathogen Interaction: Alternatives to Classical Antibiotics to Combat Drug-Resistant Superbugs.Trends in pharmacological sciences · 2017Review
- Antibiotics in the clinical pipeline at the end of 2015.The Journal of antibiotics · 2017Review
- Environmental fatty acids enable emergence of infectious Staphylococcus aureus resistant to FASII-targeted antimicrobials.Nature communications · 2016Article
- Review
- A Pathogen-Selective Antibiotic Minimizes Disturbance to the Microbiome.Antimicrobial agents and chemotherapy · 2016Article
- Biochemical Roles for Conserved Residues in the Bacterial Fatty Acid-binding Protein Family.The Journal of biological chemistry · 2016Article
- Resistance Mechanisms and the Future of Bacterial Enoyl-Acyl Carrier Protein Reductase (FabI) Antibiotics.Cold Spring Harbor perspectives in medicine · 2016Review
- Activation of Exogenous Fatty Acids to Acyl-Acyl Carrier Protein Cannot Bypass FabI Inhibition in Neisseria.The Journal of biological chemistry · 2016Article
- How bacterial pathogens eat host lipids: implications for the development of fatty acid synthesis therapeutics.The Journal of biological chemistry · 2015Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
This study examines the alteration in Staphylococcus aureus gene expression following treatment with the type 2 fatty acid synthesis inhibitor AFN-1252. An Affymetrix array study showed that AFN-1252 rapidly increased the expression of fatty acid synthetic genes and repressed the expression of virulence genes controlled by the SaeRS 2-component regulator in exponentially growing cells. AFN-1252 did not alter virulence mRNA levels in a saeR deletion strain or in strain Newman expressing a constitutively active SaeS kinase. AFN-1252 caused a more pronounced increase in fabH mRNA levels in cells entering stationary phase, whereas the depression of virulence factor transcription was attenuated. The effect of AFN-1252 on gene expression in vivo was determined using a mouse subcutaneous granuloma infection model. AFN-1252 was therapeutically effective, and the exposure (area under the concentration-time curve from 0 to 48 h [AUC(0-48)]) of AFN-1252 in the pouch fluid was comparable to the plasma levels in orally dosed animals. The inhibition of fatty acid biosynthesis by AFN-1252 in the infected pouches was signified by the substantial and sustained increase in fabH mRNA levels in pouch-associated bacteria, whereas depression of virulence factor mRNA levels in the AFN-1252-treated pouch bacteria was not as evident as it was in exponentially growing cells in vitro. The trends in fabH and virulence factor gene expression in the animal were similar to those in slower-growing bacteria in vitro. These data indicate that the effects of AFN-1252 on virulence factor gene expression depend on the physiological state of the bacteria.
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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.