ArticleACS chemical biology2016
Potent Inhibitors of Acetyltransferase Eis Overcome Kanamycin Resistance in Mycobacterium tuberculosis.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- A proteomic and functional view of intrabacterial lipid inclusion biogenesis in mycobacteria.mBio · 2025Article
- Overcoming aminoglycoside antibiotic resistance inIn silico pharmacology · 2025Article
- Targeting Aminoglycoside Acetyltransferase Activity of Mycobacterium tuberculosis (H37Rv) Derived Eis (Enhanced Intracellular Survival) Protein with Quercetin.The protein journal · 2024Article
- Restoring susceptibility to aminoglycosides: identifying small molecule inhibitors of enzymatic inactivation.RSC medicinal chemistry · 2023Review
- Discovery and Mechanistic Analysis of Structurally Diverse Inhibitors of Acetyltransferase Eis among FDA-Approved Drugs.Biochemistry · 2023Article
- Discovery and development of inhibitors of acetyltransferase Eis to combat Mycobacterium tuberculosis.Methods in enzymology · 2023Article
- Discovery of substituted benzyloxy-benzylamine inhibitors of acetyltransferase Eis and their anti-mycobacterial activity.European journal of medicinal chemistry · 2022Article
- HowFrontiers in cellular and infection microbiology · 2022Review
- Structure-based design of haloperidol analogues as inhibitors of acetyltransferase Eis fromRSC medicinal chemistry · 2021Article
- Structure-Guided Optimization of Inhibitors of Acetyltransferase Eis fromACS chemical biology · 2020Article
- Probing the Robustness of Inhibitors of Tuberculosis Aminoglycoside Resistance Enzyme Eis by Mutagenesis.ACS infectious diseases · 2019Article
- Translational control of antibiotic resistance.Open biology · 2019Review
- Mycobacterial Aminoglycoside Acetyltransferases: A Little of Drug Resistance, and a Lot of Other Roles.Frontiers in microbiology · 2019Article
- Potent 1,2,4-Triazino[5,6 b]indole-3-thioether Inhibitors of the Kanamycin Resistance Enzyme Eis from Mycobacterium tuberculosis.ACS infectious diseases · 2018Article
- Comprehensive review of chemical strategies for the preparation of new aminoglycosides and their biological activities.Chemical Society reviews · 2018Review
- Acetylation by Eis and Deacetylation by Rv1151c of Mycobacterium tuberculosis HupB: Biochemical and Structural Insight.Biochemistry · 2018Article
- The Role of Antibiotic-Target-Modifying and Antibiotic-Modifying Enzymes inFrontiers in microbiology · 2018Review
- Interfering With DNA Decondensation as a Strategy Against Mycobacteria.Frontiers in microbiology · 2018Article
- Combating Enhanced Intracellular Survival (Eis)-Mediated Kanamycin Resistance of Mycobacterium tuberculosis by Novel Pyrrolo[1,5-a]pyrazine-Based Eis Inhibitors.ACS infectious diseases · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
A major cause of tuberculosis (TB) resistance to the aminoglycoside kanamycin (KAN) is the Mycobacterium tuberculosis (Mtb) acetyltransferase Eis. Upregulation of this enzyme is responsible for inactivation of KAN through acetylation of its amino groups. A 123 000-compound high-throughput screen (HTS) yielded several small-molecule Eis inhibitors that share an isothiazole S,S-dioxide heterocyclic core. These were investigated for their structure-activity relationships. Crystal structures of Eis in complex with two potent inhibitors show that these molecules are bound in the conformationally adaptable aminoglycoside binding site of the enzyme, thereby obstructing binding of KAN for acetylation. Importantly, we demonstrate that several Eis inhibitors, when used in combination with KAN against resistant Mtb, efficiently overcome KAN resistance. This approach paves the way toward development of novel combination therapies against aminoglycoside-resistant TB.
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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.