ArticleAntimicrobial agents and chemotherapy2007
External guide sequences targeting the aac(6')-Ib mRNA induce inhibition of amikacin resistance.
Article in Antimicrobial agents and chemotherapy, 2007. 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.
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- Bridge nucleic acid/DNA gapmers as inhibitors of gene expression by multiple antisense mechanisms.Research square · 2025Article
- Antibiotic resistance in agriculture: Perspectives on upcoming strategies to overcome upsurge in resistance.Current research in microbial sciences · 2021Review
- Silencing Antibiotic Resistance with Antisense Oligonucleotides.Biomedicines · 2021Review
- Viruses of protozoan parasites and viral therapy: Is the time now right?Virology journal · 2020Review
- Bridged Nucleic Acids Reloaded.Molecules (Basel, Switzerland) · 2019Review
- Identification of theFrontiers in microbiology · 2018Article
- Amikacin: Uses, Resistance, and Prospects for Inhibition.Molecules (Basel, Switzerland) · 2017Review
- Assessment of configurations and chemistries of bridged nucleic acids-containing oligomers as external guide sequences: a methodology for inhibition of expression of antibiotic resistance genes.Biology methods & protocols · 2016Article
- RNase P-Mediated Sequence-Specific Cleavage of RNA by Engineered External Guide Sequences.Biomolecules · 2015Review
- External guide sequence technology: a path to development of novel antimicrobial therapeutics.Annals of the New York Academy of Sciences · 2015Review
- Inhibitors of the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] identified by in silico molecular docking.Bioorganic & medicinal chemistry letters · 2013Article
- Strategies to overcome the action of aminoglycoside-modifying enzymes for treating resistant bacterial infections.Future medicinal chemistry · 2013Review
- Rise and dissemination of aminoglycoside resistance: the aac(6')-Ib paradigm.Frontiers in microbiology · 2013Article
- Understanding and overcoming aminoglycoside resistance caused by N-6'-acetyltransferase.MedChemComm · 2012Article
- Inhibition of cell division induced by external guide sequences (EGS Technology) targeting ftsZ.PloS one · 2012Article
- Aminoglycoside modifying enzymes.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2010Review
- Inhibition of aac(6')-Ib-mediated amikacin resistance by nuclease-resistant external guide sequences in bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Inactivation of expression of several genes in a variety of bacterial species by EGS technology.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Rapid selection of accessible and cleavable sites in RNA by Escherichia coli RNase P and random external guide sequences.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The dissemination of AAC(6')-I-type acetyltransferases have rendered amikacin and other aminoglycosides all but useless in some parts of the world. Antisense technologies could be an alternative to extend the life of these antibiotics. External guide sequences are short antisense oligoribonucleotides that induce RNase P-mediated cleavage of a target RNA by forming a precursor tRNA-like complex. Thirteen-nucleotide external guide sequences complementary to locations within five regions accessible for interaction with antisense oligonucleotides in the mRNA that encodes AAC(6')-Ib were analyzed. While small variations in the location targeted by different external guide sequences resulted in big changes in efficiency of binding to native aac(6')-Ib mRNA, most of them induced high levels of RNase P-mediated cleavage in vitro. Recombinant plasmids coding for selected external guide sequences were introduced into Escherichia coli harboring aac(6')-Ib, and the transformant strains were tested to determine their resistance to amikacin. The two external guide sequences that showed the strongest binding efficiency to the mRNA in vitro, EGSC3 and EGSA2, interfered with expression of the resistance phenotype at different degrees. Growth curve experiments showed that E. coli cells harboring a plasmid coding for EGSC3, the external guide sequence with the highest mRNA binding affinity in vitro, did not grow for at least 300 min in the presence of 15 mug of amikacin/ml. EGSA2, which had a lower mRNA-binding affinity in vitro than EGSC3, inhibited the expression of amikacin resistance at a lesser level; growth of E. coli harboring a plasmid coding for EGSA2, in the presence of 15 mug of amikacin/ml was undetectable for 200 min but reached an optical density at 600 nm of 0.5 after 5 h of incubation. Our results indicate that the use of external guide sequences could be a viable strategy to preserve the efficacy of amikacin.
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Registered trials
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