ArticleBiochemistry2012
Aminoglycoside multiacetylating activity of the enhanced intracellular survival protein from Mycobacterium smegmatis and its inhibition.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 48 citations in OpenAlex.
- Microevolutionary models and multi-omics analysis uncover the cross-drug resistance characteristics of capreomycin-selectedCurrent research in microbial sciences · 2025Article
- The implication of Mycobacterium tuberculosis-mediated metabolism of targeted xenobiotics.Nature reviews. 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
- Tools to Alleviate the Drug Resistance inMolecules (Basel, Switzerland) · 2022Review
- Increased whiB7 expression and antibiotic resistance in Mycobacterium chelonae carrying two prophages.BMC microbiology · 2021Article
- Structure-Guided Optimization of Inhibitors of Acetyltransferase Eis fromACS chemical biology · 2020Article
- Small-Molecule Acetylation by GCN5-RelatedMicrobiology and molecular biology reviews : MMBR · 2020Review
- Mycobacterial Aminoglycoside Acetyltransferases: A Little of Drug Resistance, and a Lot of Other Roles.Frontiers in microbiology · 2019Article
- Article
- Evaluation of Aminoglycoside and Carbapenem Resistance in a Collection of Drug-Resistant Pseudomonas aeruginosa Clinical Isolates.Microbial drug resistance (Larchmont, N.Y.) · 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
- Eis, a novel family of arylalkylamine N-acetyltransferase (EC 2.3.1.87).Scientific reports · 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
- Sulfonamide-Based Inhibitors of Aminoglycoside Acetyltransferase Eis Abolish Resistance to Kanamycin in Mycobacterium tuberculosis.Journal of medicinal chemistry · 2016Article
- Discovery and Optimization of Two Eis Inhibitor Families as Kanamycin Adjuvants against Drug-ResistantACS medicinal chemistry letters · 2016Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The enhanced intracellular survival (Eis) protein improves the survival of Mycobacterium smegmatis (Msm) in macrophages and functions as the acetyltransferase responsible for kanamycin A resistance, a hallmark of extensively drug-resistant (XDR) tuberculosis, in a large number of Mycobacterium tuberculosis (Mtb) clinical isolates. We recently demonstrated that Eis from Mtb (Eis_Mtb) efficiently multiacetylates a variety of aminoglycoside (AG) antibiotics. Here, to gain insight into the origin of substrate selectivity of AG multiacetylation by Eis, we analyzed AG acetylation by Eis_Msm, investigated its inhibition, and compared these functions to those of Eis_Mtb. Even though for several AGs the multiacetylation properties of Eis_Msm and Eis_Mtb are similar, there are three major differences. (i) Eis_Msm diacetylates apramycin, a conformationally constrained AG, which Eis_Mtb cannot modify. (ii) Eis_Msm triacetylates paromomycin, which can be only diacetylated by Eis_Mtb. (iii) Eis_Msm only monoacetylates hygromycin, a structurally unique AG that is diacetylated by Eis_Mtb. Several nonconserved amino acid residues lining the AG-binding pocket of Eis are likely responsible for these differences between the two Eis homologues. Specifically, we propose that because the AG-binding pocket of Eis_Msm is more open than that of Eis_Mtb, it accommodates apramycin for acetylation in Eis_Msm, but not in Eis_Mtb. We also demonstrate that inhibitors of Eis_Mtb that we recently discovered can inhibit Eis_Msm activity. These observations help define the structural origins of substrate preference among Eis homologues and suggest that Eis_Mtb inhibitors may be applied against all pathogenic mycobacteria to overcome AG resistance caused by Eis upregulation.
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