ArticleChemical science2025
Binding assays enable discovery of Tet(X) inhibitors that combat tetracycline destructase resistance.
Article in Chemical science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Evolution, Mechanisms, and Therapeutic Implications of Mobile Tetracycline Destructases.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- The Role of Natural Flavonoid Quercetin in Combating Tet(X3)/Tet(X4)-Positive Bacterial Infections.Microorganisms · 2026Article
- Evidence that SmTetX is not a tetracycline resistance determinant.Microbiology spectrum · 2026Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Tet(X) flavin-dependent monooxygenases enable tetracycline antibiotic resistance by catalysing inactivating hydroxylation, so preventing inhibition of bacterial ribosomes. Tet(X) resistance is growing rapidly, threatening the efficacy of important last-resort tetracyclines such as tigecycline. Tet(X) inhibitors have potential to protect tetracyclines in combination therapies, but their discovery has been hampered by lack of high-throughput assays. We report the development of an efficient fluorescence polarisation Tet(X) binding assay employing a tetramethylrhodamine-glycyl-minocycline conjugate that enables inhibitor discovery. The assay was applied to tetracycline substrates and reported inhibitors, providing insight into their binding modes. Screening of a bioactive molecule library identified novel Tet(X) inhibitors, including psychoactive phenothiazine derivatives and the 5-HT
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Registered trials
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