ArticleEuropean journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology2016
Evaluation of the characteristics of leucyl-tRNA synthetase (LeuRS) inhibitor AN3365 in combination with different antibiotic classes.
Article in European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Elution kinetics and antimicrobial efficacy of high-dose gram-negative antibiotic-loaded acrylic cement: an in vitro and in vivo study.BMC microbiology · 2026Article
- Genome-wide Screening of the Escherichia coli Keio Knockout Collection Identifies Genetic Determinants of Epetraborole Hypersusceptibility.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Article
- Time-Dependent Inhibition of Leucyl-tRNA-Synthetase (LeuRS): Insight into Target Vulnerability.ACS infectious diseases · 2025Article
- Article
- Identification and Characterization of Chemical Compounds that Inhibit Leucyl-tRNA Synthetase fromCurrent drug discovery technologies · 2020Article
- Review
- Antibacterial Activity and Mode of Action of a Sulfonamide-Based Class of Oxaborole Leucyl-tRNA-Synthetase Inhibitors.ACS infectious diseases · 2019Article
- Access to high-impact mutations constrains the evolution of antibiotic resistance in soft agar.Scientific reports · 2018Article
- Subinhibitory Concentrations of Bacteriostatic Antibiotics InduceAntimicrobial agents and chemotherapy · 2017Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aminoacyl tRNA synthetases are enzymes involved in the key process of coupling an amino acid to its cognate tRNA. AN3365 is a novel antibiotic that specifically targets leucyl-tRNA synthetase, whose development was halted after evaluation in phase II clinical trials owing to the rapid selection of resistance. In an attempt to bring AN3365 back into the developmental pipeline we have evaluated the efficacy of AN3365 in combination with different classes of antibiotic and characterized its mechanism of action. Although we detect no synergy or antagonism in combination with a range of antibiotic classes, a combination of AN3365 with colistin reduces the accumulation of AN3365-resistant and colistin resistance mutations. We also demonstrate that treatment with AN3365 results in the dramatic accumulation of the alarmone (p)ppGpp, the effector of the stringent response-a key player in antibiotic tolerance.
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Registered trials
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