ArticleThe Journal of antibiotics2019
Synergistic enhancement of beta-lactam antibiotics by modified tunicamycin analogs TunR1 and TunR2.
Article in The Journal of antibiotics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The trial behind it
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Over-expression, purification, and kinetic analysis ofJournal of enzyme inhibition and medicinal chemistry · 2026Article
- Synergistic action of peptidoglycan and teichoic acid synthesis inhibitors leads to cell death by oxidative damage.Communications biology · 2026Article
- Natural Products as Potentiators of β-Lactam Antibiotics: A Review of Mechanisms, Advances, and Future Directions.Antioxidants (Basel, Switzerland) · 2026Review
- TunR2, a novel mode-of-action tunicamycin-type antibiotic: Pharmacokinetics in C57BL/6 mouse and Holstein cattle.PloS one · 2025Article
- Antibiotics: From Mechanism of Action to Resistance and Beyond.Indian journal of microbiology · 2024Review
- The tunicamycin derivative TunR2 exhibits potent antibiotic properties with low toxicity in an in vivo Mycobacterium marinum-zebrafish TB infection model.The Journal of antibiotics · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The β-lactams are the most widely used group of antibiotics in human health and agriculture, but this is under threat due to the persistent rise of pathogenic resistance. Several compounds, including tunicamycin (TUN), can enhance the antibacterial activity of the β-lactams to the extent of overcoming resistance, but the mammalian toxicity of TUN has precluded its use in this role. Selective hydrogenation of TUN produces modified compounds (TunR1 and TunR2), which retain the enhancement of β-lactams while having much lower mammalian toxicity. Here we show that TunR1 and TunR2 enhance the antibacterial activity of multiple β-lactam family members, including penems, cephems, and third-generation penicillins, to a similar extent as does the native TUN. Eleven of the β-lactams tested were enhanced from 2 to >256-fold against Bacillus subtilis, with comparable results against a penicillin G-resistant strain. The most significant enhancements were obtained with third-generation aminothiazolidyl cephems, including cefotaxime, ceftazidime, and cefquinome. These results support the potential of low toxicity tunicamycin analogs (TunR1 and TunR2) as clinically valid, synergistic enhancers for a broad group of β-lactam antibiotics.
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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.