ArticleAntimicrobial agents and chemotherapy2016
Combining the FtsZ-Targeting Prodrug TXA709 and the Cephalosporin Cefdinir Confers Synergy and Reduces the Frequency of Resistance in Methicillin-Resistant Staphylococcus aureus.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Antibacterial drug discovery: challenges and preclinical promises from synthetic small molecules.Chemical Society reviews · 2026Review
- The global resistance problem and the clinical antibacterial pipeline.Nature reviews. Microbiology · 2025Review
- Review
- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
- QSAR analysis of five generations of cephalosporins to establish the structural basis of activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus.Molecular diversity · 2024Article
- A FtsZ Inhibitor That Can Utilize Siderophore-Ferric Iron Uptake Transporter Systems for Activity against Gram-Negative Bacterial Pathogens.Antibiotics (Basel, Switzerland) · 2024Article
- Models versus pathogens: how conserved is the FtsZ in bacteria?Bioscience reports · 2023Review
- Antibacterial Activity of an FtsZ Inhibitor Celastrol and Its Synergistic Effect with Vancomycin against EnterococciMicrobiology spectrum · 2023Article
- Combination with a FtsZ inhibitor potentiates the in vivo efficacy of oxacillin against methicillin-resistantMedicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2022Article
- The Search for Antibacterial Inhibitors Targeting Cell Division Protein FtsZ at Its Nucleotide and Allosteric Binding Sites.Biomedicines · 2022Review
- Evaluation of 2,6-difluoro-3-(oxazol-2-ylmethoxy)benzamide chemotypes as Gram-negative FtsZ inhibitors.The Journal of antibiotics · 2022Article
- Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria.Microorganisms · 2022Review
- Impact of FtsZ Inhibition on the Localization of the Penicillin Binding Proteins in Methicillin-Resistant Staphylococcus aureus.Journal of bacteriology · 2021Article
- Targeting the FtsZ Allosteric Binding Site with a Novel Fluorescence Polarization Screen, Cytological and Structural Approaches for Antibacterial Discovery.Journal of medicinal chemistry · 2021Article
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
- Antimicrobial Action and Reversal of Resistance in MRSA by Difluorobenzamide Derivatives Targeted at FtsZ.Antibiotics (Basel, Switzerland) · 2020Article
- Critical analysis of antibacterial agents in clinical development.Nature reviews. Microbiology · 2020Review
- Targeting Bacterial Cell Division: A Binding Site-Centered Approach to the Most Promising Inhibitors of the Essential Protein FtsZ.Antibiotics (Basel, Switzerland) · 2020Review
- Crystal structures of the cell-division protein FtsZ from Klebsiella pneumoniae and Escherichia coli.Acta crystallographica. Section F, Structural biology communications · 2020Article
- Structure-Guided Design of a Fluorescent Probe for the Visualization of FtsZ in Clinically Important Gram-Positive and Gram-Negative Bacterial Pathogens.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Combination therapy of bacterial infections with synergistic drug partners offers distinct advantages over monotherapy. Among these advantages are (i) a reduction of the drug dose required for efficacy, (ii) a reduced potential for drug-induced toxicity, and (iii) a reduced potential for the emergence of resistance. Here, we describe the synergistic actions of the third-generation oral cephalosporin cefdinir and TXA709, a new, FtsZ-targeting prodrug that we have developed with improved pharmacokinetics and enhanced in vivo efficacy against methicillin-resistant Staphylococcus aureus (MRSA) relative to earlier agents. We show that the active product of TXA709 (TXA707) acts synergistically with cefdinir in vitro against clinical isolates of MRSA, vancomycin-intermediate S. aureus (VISA), vancomycin-resistant S. aureus (VRSA), and linezolid-resistant S. aureus (LRSA). In addition, relative to TXA707 alone, the combination of TXA707 and cefdinir significantly reduces or eliminates the detectable emergence of resistance. We also demonstrate synergy in vivo with oral administration of the prodrug TXA709 and cefdinir in mouse models of both systemic and tissue (thigh) infections with MRSA. This synergy reduces the dose of TXA709 required for efficacy 3-fold. Viewed as a whole, our results highlight the potential of TXA709 and cefdinir as a promising combination for the treatment of drug-resistant staphylococcal infections.
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