2014
DOI: 10.1021/ja4115924
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Baulamycins A and B, Broad-Spectrum Antibiotics Identified as Inhibitors of Siderophore Biosynthesis in Staphylococcus aureus and Bacillus anthracis

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… Show more

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Cited by 79 publications
(78 citation statements)
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“…A compound, flucytosine, which inhibits PvdS, a promoter of virulence genes including pyoverdine synthesis genes, was identified and flucytosine reduced P. aeruginosa pathogenicity in a mouse model (Imperi et al, 2013). Baulamycin A, a broad-spectrum antibiotic produced by a Streptomyces spp., acts as a competitive inhibitor of the Staphylococcus aureus SbnE synthetase, involved in the NRPS-independent synthesis of staphyloferrin B, and impedes the growth of Staphylococcus aureus under iron restriction (Tripathi et al, 2014). This report demonstrates the enormous potential of targeting siderophore biosynthesis pathways using these natural baulamycins, which can be further modified to enhance efficacy and specificity.…”
Section: Novel Therapeutic Strategies Targeting Iron Acquisition In Cmentioning
confidence: 86%
“…A compound, flucytosine, which inhibits PvdS, a promoter of virulence genes including pyoverdine synthesis genes, was identified and flucytosine reduced P. aeruginosa pathogenicity in a mouse model (Imperi et al, 2013). Baulamycin A, a broad-spectrum antibiotic produced by a Streptomyces spp., acts as a competitive inhibitor of the Staphylococcus aureus SbnE synthetase, involved in the NRPS-independent synthesis of staphyloferrin B, and impedes the growth of Staphylococcus aureus under iron restriction (Tripathi et al, 2014). This report demonstrates the enormous potential of targeting siderophore biosynthesis pathways using these natural baulamycins, which can be further modified to enhance efficacy and specificity.…”
Section: Novel Therapeutic Strategies Targeting Iron Acquisition In Cmentioning
confidence: 86%
“…An activity assay was developed for high throughput screening (originally intended for NRPS enzymes) that converts the pyrophosphate to inorganic phosphate which is detected by malachite green [60]. A screen was designed to only identify compounds from a marine microbial-derived natural product library that inhibited both SbnE and AsbA [61]. The result was the identification of the baulamycins (Figure 8C) as competitive, reversible inhibitors with IC 50 values in the micromolar range.…”
Section: Inhibitors Of Nis Biosynthesismentioning
confidence: 99%
“…B. Condensation of citric acid (blue) with spermidine (green) by NIS synthetase AsbA from B. anthrasis for the production of petrobactin. C. Micromolar antibiotic inhibitor of SbnE and AsbA [61]. …”
Section: Figurementioning
confidence: 99%
“…Among these pathogens are the Gram-positive bacteria Streptococcus pneumoniae and Bacillus anthracis. Both are associated with a decrease in the potency of available treatments [1][2][3][4][5], and at the forefront of continuing efforts to discover new antibiotics by targeting novel enzymes in essential metabolic pathways [6,7]. One such pathway is the de novo purine-biosynthesis pathway, in which organisms build the foundation of purine based nucleotides, inosine monophosphate (IMP), from 5-phosphoribosyl pyrophosphate (PPRP), a process essential for DNA/RNA synthesis and bacterial virulence in human serum [8].…”
Section: Introductionmentioning
confidence: 99%