ArticleAntimicrobial agents and chemotherapy2015
FabH mutations confer resistance to FabF-directed antibiotics in Staphylococcus aureus.
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 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Anticancer compounds from Streptomyces: insights from metagenomics and mechanistic perspective.Folia microbiologica · 2025Review
- The serine protease HtrA regulates Group B Streptococcus virulence and affects the host response to infection.PLoS pathogens · 2025Article
- Direct prediction of antimicrobial resistance inFrontiers in microbiology · 2024Article
- Mining Fatty Acid Biosynthesis for New Antimicrobials.Annual review of microbiology · 2022Review
- Article
- Semisynthesis and Biological Evaluation of Platencin Thioether Derivatives: Dual FabF and FabH Inhibitors against MRSA.ACS medicinal chemistry letters · 2021Article
- Isotopically Labeled Desthiobiotin Azide (isoDTB) Tags Enable Global Profiling of the Bacterial Cysteinome.Angewandte Chemie (International ed. in English) · 2020Article
- Late-Stage Functionalization of Platensimycin Leading to Multiple Analogues with Improved Antibacterial Activity in Vitro and in Vivo.Journal of medicinal chemistry · 2019Article
- Platensimycin and platencin: Inspirations for chemistry, biology, enzymology, and medicine.Biochemical pharmacology · 2017Review
- A genomics-led approach to deciphering the mechanism of thiotetronate antibiotic biosynthesis.Chemical science · 2016Article
- Identification of Thiotetronic Acid Antibiotic Biosynthetic Pathways by Target-directed Genome Mining.ACS chemical biology · 2015Article
- Chlamydia trachomatis Scavenges Host Fatty Acids for Phospholipid Synthesis via an Acyl-Acyl Carrier Protein Synthetase.The Journal of biological chemistry · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Delineating the mechanisms for genetically acquired antibiotic resistance is a robust approach to target validation and anticipates the evolution of clinical drug resistance. This study defines a spectrum of mutations in fabH that render Staphylococcus aureus resistant to multiple natural products known to inhibit the elongation condensing enzyme (FabF) of bacterial type II fatty acid synthesis. Twenty independently isolated clones resistant to platensimycin, platencin, or thiolactomycin were isolated. All mutants selected against one antibiotic were cross-resistant to the other two antibiotics. Mutations were not detected in fabF, but the resistant strains harbored missense mutations in fabH. The altered amino acids clustered in and around the FabH active-site tunnel. The mutant FabH proteins were catalytically compromised based on the low activities of the purified enzymes, a fatty acid-dependent growth phenotype, and elevated expression of the fabHF operon in the mutant strains. Independent manipulation of fabF and fabH expression levels showed that the FabH/FabF activity ratio was a major determinant of antibiotic sensitivity. Missense mutations that reduce FabH activity are sufficient to confer resistance to multiple antibiotics that bind to the FabF acyl-enzyme intermediate in S. aureus.
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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.