ArticleJournal of the American Chemical Society2014
Baulamycins A and B, broad-spectrum antibiotics identified as inhibitors of siderophore biosynthesis in Staphylococcus aureus and Bacillus anthracis.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 92 citations in OpenAlex.
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- Natural Products Repository of Costa Rica (NAPRORE-CR): An Open-Access Database.Journal of chemical information and modeling · 2025Article
- Mechanism, Efficacy, and Safety of Natural Antibiotics.Antibiotics (Basel, Switzerland) · 2025Review
- First-in-class inhibitors of SbnA reduce siderophore production in Staphylococcus aureus.The FEBS journal · 2025Article
- Isolation of Verrucosins A-E from a MarineJournal of natural products · 2025Article
- Targeting Siderophore Biosynthesis to Thwart Microbial Growth.International journal of molecular sciences · 2025Review
- Syntheses of Marine Natural Products via Matteson Homologations and Related Processes.Marine drugs · 2025Review
- Exploiting haem-iron dependence of nontypeableFrontiers in cellular and infection microbiology · 2025Review
- Microbial Siderophores: A New Insight on Healthcare Applications.BME frontiers · 2025Review
- DecipheringmSystems · 2024Article
- Deciphering the genomic character of the multidrug-resistantAIMS microbiology · 2024Article
- A look around the West Indies: The spices of life are secondary metabolites.Bioorganic & medicinal chemistry · 2020Review
- Tackling Antibiotic Resistance with Compounds of Natural Origin: A Comprehensive Review.Biomedicines · 2020Review
- Creating and screening natural product libraries.Natural product reports · 2020Review
- Resistance of Gram-Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches.Molecules (Basel, Switzerland) · 2020Review
- Iron Metabolism at the Interface between Host and Pathogen: From Nutritional Immunity to Antibacterial Development.International journal of molecular sciences · 2020Review
- Stereoselective Synthesis of Baulamycin A.The Journal of organic chemistry · 2020Article
- Scavenging Bacterial Siderophores with Engineered Lipocalin Proteins as an Alternative Antimicrobial Strategy.Chembiochem : a European journal of chemical biology · 2020Review
- Adipostatins E-J, New Potent Antimicrobials Identified as Inhibitors of Coenzyme-A Biosynthesis.Tetrahedron letters · 2020Article
- Development of a High-Throughput Biochemical Assay to Screen for Inhibitors of Aerobactin Synthetase IucA.SLAS discovery : advancing life sciences R & D · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Siderophores are high-affinity iron chelators produced by microorganisms and frequently contribute to the virulence of human pathogens. Targeted inhibition of the biosynthesis of siderophores staphyloferrin B of Staphylococcus aureus and petrobactin of Bacillus anthracis hold considerable potential as a single or combined treatment for methicillin-resistant S. aureus (MRSA) and anthrax infection, respectively. The biosynthetic pathways for both siderophores involve a nonribosomal peptide synthetase independent siderophore (NIS) synthetase, including SbnE in staphyloferrin B and AsbA in petrobactin. In this study, we developed a biochemical assay specific for NIS synthetases to screen for inhibitors of SbnE and AsbA against a library of marine microbial-derived natural product extracts (NPEs). Analysis of the NPE derived from Streptomyces tempisquensis led to the isolation of the novel antibiotics baulamycins A (BmcA, 6) and B (BmcB, 7). BmcA and BmcB displayed in vitro activity with IC50 values of 4.8 μM and 19 μM against SbnE and 180 μM and 200 μM against AsbA, respectively. Kinetic analysis showed that the compounds function as reversible competitive enzyme inhibitors. Liquid culture studies with S. aureus , B. anthracis , E. coli , and several other bacterial pathogens demonstrated the capacity of these natural products to penetrate bacterial barriers and inhibit growth of both Gram-positive and Gram-negative species. These studies provide proof-of-concept that natural product inhibitors targeting siderophore virulence factors can provide access to novel broad-spectrum antibiotics, which may serve as important leads for the development of potent anti-infective agents.
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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.