Cited by 32Antibiotic Resistance in BacteriaAntibiotics Pharmacokinetics and EfficacyBacterial Genetics and Biotechnology

Potentiation of Antibacterial Activity of the MB-1 Siderophore-Monobactam Conjugate Using an Efflux Pump Inhibitor

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Tomaras, Andrew P., Crandon, Jared L., McPherson, Craig J., Nicolau, David P.·2015·Antimicrobial Agents and Chemotherapy

Abstract

Preliminary enthusiasm over the encouraging spectrum and in vitro activities of siderophore conjugates, such as MB-1, was recently tempered by unexpected variability in in vivo efficacy. The need for these conjugates to compete for iron with endogenously produced siderophores has exposed a significant liability for this novel antibacterial strategy. Here, we have exploited dependence on efflux for siderophore secretion in Pseudomonas aeruginosa and provide evidence that efflux inhibition may circumvent this in vivo -relevant resistance liability.

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Crossref · 10.1128/aac.04172-14

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18 of 18 references verified0 citation errors · 0 not checkable

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  • Apart from binding their primary ligand, FeEnt, with high affinity, and its aposiderophore Ent with 100-200-fold lower affinity, KpnFepA_1658, KpnIroN, and KpnFepA_4984 showed different preferences for ferric catecholate complexes and siderophore antibiotics cefiderocol [FeFDC] and FeMB-1.

    “Apart from binding their primary ligand, FeEnt, with high affinity, and its aposiderophore Ent with 100-200-fold lower affinity (38), KpnFepA_1658, KpnIroN, and KpnFepA_4984 showed different preferences for ferric catecholate complexes and siderophore antibiotics cefiderocol [FeFDC (40,41)] and FeMB-1 (42,43):”

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Authors
Tomaras, A. P., Crandon, J. L., McPherson, C. J., & Nicolau, D. P.
Affiliations
  • Pfizer (United States) (US)
  • Hartford Hospital (US)
Venue
Antimicrobial Agents and Chemotherapy
Published
2015-04
Volume
59
Issue
4
Pages
2439-2442
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
OpenAlex
W2089873723
Cited by
32
References
18
Citations by year
2026: 1 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 2
FWCI
1.52
Type
journal article
Language
en
Open access
Locations
  • Antimicrobial Agents and Chemotherapy (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
  • Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
mb-1, efflux pump inhibitors, Pseudomonas aeruginosa, siderophore secretion, iron acquisition, antibacterial activity, in vivo efficacy
MeSH terms
Anti-Bacterial Agents, Microbial Sensitivity Tests, Monobactams, Mutation, Pseudomonas aeruginosa, Pyridones, Reserpine, Siderophores, ATP-Binding Cassette Transporters, Drug Resistance, Bacterial

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