ArticleProceedings of the National Academy of Sciences of the United States of America2009
Overexpression of the chromosomally encoded aminoglycoside acetyltransferase eis confers kanamycin resistance in Mycobacterium tuberculosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers, 2 of them syntheses that pooled it.
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171 citing papers in PubMed, 2 syntheses or guidelines pooled it, 329 citations in OpenAlex.
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- Suppressing Mycobacterium tuberculosis virulence and drug resistance by targeting Eis protein through computational drug discovery.Molecular diversity · 2025Article
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- Microevolutionary models and multi-omics analysis uncover the cross-drug resistance characteristics of capreomycin-selectedCurrent research in microbial sciences · 2025Article
- Overcoming aminoglycoside antibiotic resistance inIn silico pharmacology · 2025Article
- Antibiotic resistance mediated by gene amplifications.npj antimicrobials and resistance · 2024Review
- Drug-resistant tuberculosis: a persistent global health concern.Nature reviews. Microbiology · 2024Review
- Resistome Signature and Antibiotic Resistance Mechanisms in Rhizospheric Soil Bacteriomes of Mecca Region, Saudi Arabia: Insights into Impact on Human Health.Life (Basel, Switzerland) · 2024Article
- Beyond antibiotic resistance: The whiB7 transcription factor coordinates an adaptive response to alanine starvation in mycobacteria.Cell chemical biology · 2024Article
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- How do Mutations of Mycobacterium Genes Cause Drug Resistance in Tuberculosis?Current pharmaceutical biotechnology · 2024Review
111 more citing papers are in PubMed but not listed here.
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5 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The emergence of multidrug-resistant (MDR) tuberculosis (TB) highlights the urgent need to understand the mechanisms of resistance to the drugs used to treat this disease. The aminoglycosides kanamycin and amikacin are important bactericidal drugs used to treat MDR TB, and resistance to one or both of these drugs is a defining characteristic of extensively drug-resistant TB. We identified mutations in the -10 and -35 promoter region of the eis gene, which encodes a previously uncharacterized aminoglycoside acetyltransferase. These mutations led to a 20-180-fold increase in the amount of eis leaderless mRNA transcript, with a corresponding increase in protein expression. Importantly, these promoter mutations conferred resistance to kanamycin [5 microg/mL < minimum inhibitory concentration (MIC) <or=40 microg/mL] but not to amikacin (MIC <4 microg/mL). Additionally, 80% of clinical isolates examined in this study that exhibited low-level kanamycin resistance harbored eis promoter mutations. These results have important clinical implications in that clinical isolates determined to be resistant to kanamycin may not be cross-resistant to amikacin, as is often assumed. Molecular detection of eis mutations should distinguish strains resistant to kanamycin and those resistant to kanamycin and amikacin. This may help avoid excluding a potentially effective drug from a treatment regimen for drug-resistant TB.
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