ArticleJournal of the American Chemical Society2018
Esterase-Catalyzed Siderophore Hydrolysis Activates an Enterobactin-Ciprofloxacin Conjugate and Confers Targeted Antibacterial Activity.
Article in Journal of the American Chemical Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 140 citations in OpenAlex.
- Iron starvation induced by vacidobactin A impairs the growth of pyoverdine-deficientMicrobiology spectrum · 2026Article
- Bacterial Adaptive Responses to Green and Chemically Synthesized Silver Nanoparticles: Implications for Resistance Development.Nanomaterials (Basel, Switzerland) · 2026Article
- Siderophore-Pt(IV) Conjugates as Tools to Probe Cytoplasmic Cargo Delivery to Gram-Negative Bacteria.Journal of the American Chemical Society · 2026Article
- Antibody-drug conjugates for infectious and neglected tropical diseases: chemical design principles, target biology, and translational challenges.Frontiers in chemistry · 2026Review
- Structure-Guided Development of Mycobacterial Thymidine Monophosphate Kinase (MtbTMPK) Inhibitors: Unlocking New Frontiers in Tuberculosis Research.Current topics in medicinal chemistry · 2026Review
- Stringent response-mediated ferroptosis-like death resistance underliesApplied and environmental microbiology · 2025Article
- Design, Synthesis, and Antibacterial Evaluation of Rifampicin-Siderophore Conjugates.ACS infectious diseases · 2025Article
- Commensal resilience: ancient ecological lessons for the modern microbiota.Infection and immunity · 2025Review
- Re-evaluation of theBiochemistry · 2025Article
- Article
- The Role of Bacterial Siderophores in Infection Therapy: From Anti-Infective Mechanisms to Therapeutic Advances.International journal of nanomedicine · 2025Review
- Location, Location, Location: Establishing Design Principles for New Antibacterials from Ferric Siderophore Transport Systems.Molecules (Basel, Switzerland) · 2024Review
- "Off-Label Use" of the Siderophore Enterobactin Enables Targeted Imaging of Cancer with Radioactive TiAngewandte Chemie (International ed. in English) · 2024Article
- Investigation of Siderophore-Platinum(IV) Conjugates Reveals Differing Antibacterial Activity and DNA Damage Depending on the Platinum Cargo.ACS infectious diseases · 2024Article
- Exploring the Antibacterial Activity and Cellular Fates of Enterobactin-Drug Conjugates That Target Gram-Negative Bacterial Pathogens.Accounts of chemical research · 2024Article
- In vitro and in silico studies of enterobactin-inspired Ciprofloxacin and Fosfomycin first generation conjugates on the antibiotic resistant E. coli OQ866153.BMC microbiology · 2024Article
- Conjugation to Native and Nonnative Triscatecholate Siderophores Enhances Delivery and Antibacterial Activity of a β-Lactam to Gram-Negative Bacterial Pathogens.Journal of the American Chemical Society · 2024Article
- A FtsZ Inhibitor That Can Utilize Siderophore-Ferric Iron Uptake Transporter Systems for Activity against Gram-Negative Bacterial Pathogens.Antibiotics (Basel, Switzerland) · 2024Article
- Benzothiazole DNA gyrase inhibitors and their conjugates with siderophore mimics: design, synthesis and evaluation.RSC advances · 2024Article
- Network depth affects inference of gene sets from bacterial transcriptomes using denoising autoencoders.Bioinformatics advances · 2024Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Enteric Gram-negative bacteria, including Escherichia coli, biosynthesize and deploy the triscatecholate siderophore enterobactin (Ent) in the vertebrate host to acquire iron, an essential nutrient. We report that Ent-Cipro, a synthetic siderophore-antibiotic conjugate based on the native Ent platform that harbors an alkyl linker at one of the catechols with a ciprofloxacin cargo attached, affords targeted antibacterial activity against E. coli strains that express the pathogen-associated iroA gene cluster. Attachment of the siderophore to ciprofloxacin, a DNA gyrase inhibitor and broad-spectrum antibiotic that is used to treat infections caused by E. coli, generates an inactive prodrug and guides the antibiotic into the cytoplasm of bacteria that express the Ent uptake machinery (FepABCDG). Intracellular hydrolysis of the siderophore restores the activity of the antibiotic. Remarkably, Fes, the cytoplasmic Ent hydrolase expressed by all E. coli, does not contribute to Ent-Cipro activation. Instead, this processing step requires IroD, a cytoplasmic hydrolase that is expressed only by E. coli that harbor the iroA gene cluster and are predominantly pathogenic. In the uropathogenic E. coli UTI89 and CFT073, Ent-Cipro provides antibacterial activity comparable to unmodified ciprofloxacin. This work highlights the potential of leveraging and targeting pathogen-associated microbial enzymes in narrow-spectrum antibacterial approaches. Moreover, because E. coli include harmless gut commensals as well as resident microbes that can contribute to disease, Ent-Cipro may provide a valuable chemical tool for strain-selective modulation of the microbiota.
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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.