ArticleAntimicrobial agents and chemotherapy2012
Target- and resistance-based mechanistic studies with TP-434, a novel fluorocycline antibiotic.
Article in Antimicrobial agents and chemotherapy, 2012. 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 84 papers.
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Who cites it
84 citing papers in PubMed, 160 citations in OpenAlex.
- IGNITE4: Results of a Phase 3, Randomized, Multicenter, Prospective Trial of Eravacycline vs Meropenem in the Treatment of Complicated Intraabdominal Infections.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Trial
- Randomized, Double-Blind, Placebo-Controlled Studies of the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of Eravacycline.Antimicrobial agents and chemotherapy · 2018Trial
- The Role of Pyrrolidine in Antibacterial Drug Discovery: Clinically Approved Antibiotics, Novel Derivatives, and Future Perspectives.International journal of molecular sciences · 2026Review
- Eravacycline as a Novel Option for Treating Multidrug-Resistant Gram-Negative and Gram-Positive Bacterial Infections: A Narrative Review.Journal of clinical medicine · 2026Review
- The Rise in Carbapenem-ResistantPathogens (Basel, Switzerland) · 2026Review
- Parental Tetracycline Exposure Induces Genotoxic Damage and Fitness Deficits in Daphnia magna Offspring.Environmental and molecular mutagenesis · 2026Article
- Cryo-EM reveals multiple mechanisms of ribosome inhibition by doxycycline.Nature communications · 2026Article
- Beyond β-Lactams: Defining the Role of Eravacycline in Multidrug-Resistant and Metallo-β-Lactamase-Producing Infections.Antibiotics (Basel, Switzerland) · 2026Review
- Eravacycline: From broad-spectrum coverage to novel clinical applications.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2026Review
- Binding assays enable discovery of Tet(X) inhibitors that combat tetracycline destructase resistance.Chemical science · 2025Article
- Newly developed antibiotics against multidrug-resistant and carbapenem-resistant Gram-negative bacteria: action and resistance mechanisms.Archives of microbiology · 2025Review
- Screening and comparison ofFrontiers in cellular and infection microbiology · 2025Article
- Dual role ofiMetaOmics · 2024Article
- Paenilamicins are context-specific translocation inhibitors of protein synthesis.Nature chemical biology · 2024Article
- Synthetic macrolides overcoming MLSCell discovery · 2024Article
- Third-Generation Tetracyclines: Current Knowledge and Therapeutic Potential.Biomolecules · 2024Review
- Unveiling the Secrets ofInternational journal of molecular sciences · 2024Review
- Paenilamicins from the honey bee pathogenbioRxiv : the preprint server for biology · 2024Article
- Eravacycline, the first four years: health outcomes and tolerability data for 19 hospitals in 5 U.S. regions from 2018 to 2022.Microbiology spectrum · 2024Article
- Comparison of antimicrobial activities and resistance mechanisms of eravacycline and tigecycline against clinicalFrontiers in microbiology · 2024Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TP-434 is a novel, broad-spectrum fluorocycline antibiotic with activity against bacteria expressing major antibiotic resistance mechanisms, including tetracycline-specific efflux and ribosomal protection. The mechanism of action of TP-434 was assessed using both cell-based and in vitro assays. In Escherichia coli cells expressing recombinant tetracycline resistance genes, the MIC of TP-434 (0.063 μg/ml) was unaffected by tet(M), tet(K), and tet(B) and increased to 0.25 and 4 μg/ml in the presence of tet(A) and tet(X), respectively. Tetracycline, in contrast, was significantly less potent (MIC ≥ 128 μg/ml) against E. coli cells when any of these resistance mechanisms were present. TP-434 showed potent inhibition in E. coli in vitro transcription/translation (50% inhibitory concentration [IC(50)] = 0.29 ± 0.09 μg/ml) and [(3)H]tetracycline ribosome-binding competition (IC(50) = 0.22 ± 0.07 μM) assays. The antibacterial potencies of TP-434 and all other tetracycline class antibiotics tested were reduced by 4- to 16-fold, compared to that of the wild-type control strain, against Propionibacterium acnes strains carrying a 16S rRNA mutation, G1058C, a modification that changes the conformation of the primary binding site of tetracycline in the ribosome. Taken together, the findings support the idea that TP-434, like other tetracyclines, binds the ribosome and inhibits protein synthesis and that this activity is largely unaffected by the common tetracycline resistance mechanisms.
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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.