ArticleProceedings of the National Academy of Sciences of the United States of America2009
Inhibition of aac(6')-Ib-mediated amikacin resistance by nuclease-resistant external guide sequences in bacteria.
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 36 papers.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Bridge Nucleic Acid/DNA Gapmers as Potential Inhibitors of Bacterial Gene Expression by Multiple Antisense Mechanisms: An In Vitro Study.Molecules (Basel, Switzerland) · 2025Article
- Bridge nucleic acid/DNA gapmers as inhibitors of gene expression by multiple antisense mechanisms.Research square · 2025Article
- Inhibiting Amikacin Resistance in Multidrug-Resistant Bacteria with Cadmium and Pyrithione.Current microbiology · 2025Review
- Structure-Activity Relationship of Pyrrolidine Pentamine Derivatives as Inhibitors of the Aminoglycoside 6'-Antibiotics (Basel, Switzerland) · 2024Article
- Restoring susceptibility to aminoglycosides: identifying small molecule inhibitors of enzymatic inactivation.RSC medicinal chemistry · 2023Review
- Bacterial Nosocomial Infections: Multidrug Resistance as a Trigger for the Development of Novel Antimicrobials.Antibiotics (Basel, Switzerland) · 2021Review
- Silencing Antibiotic Resistance with Antisense Oligonucleotides.Biomedicines · 2021Review
- Bridged Nucleic Acids Reloaded.Molecules (Basel, Switzerland) · 2019Review
- Restoration of susceptibility to amikacin by 8-hydroxyquinoline analogs complexed to zinc.PloS one · 2019Article
- SmallFrontiers in microbiology · 2019Article
- PNA Length Restriction of Antibacterial Activity of Peptide-PNA Conjugates inFrontiers in microbiology · 2019Article
- Identification of a small molecule inhibitor of the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] using mixture-based combinatorial libraries.International journal of antimicrobial agents · 2018Article
- Identification of theFrontiers in microbiology · 2018Article
- Amikacin: Uses, Resistance, and Prospects for Inhibition.Molecules (Basel, Switzerland) · 2017Review
- Evaluation of the electron transfer flavoprotein as an antibacterial target in Burkholderia cenocepacia.Canadian journal of microbiology · 2017Article
- 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
- Inhibition of AAC(6')-Ib-mediated resistance to amikacin in Acinetobacter baumannii by an antisense peptide-conjugated 2',4'-bridged nucleic acid-NC-DNA hybrid oligomer.Antimicrobial agents and chemotherapy · 2015Article
- External guide sequence technology: a path to development of novel antimicrobial therapeutics.Annals of the New York Academy of Sciences · 2015Review
- Public health evolutionary biology of antimicrobial resistance: priorities for intervention.Evolutionary applications · 2015Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Inhibition of bacterial gene expression by RNase P-directed cleavage is a promising strategy for the development of antibiotics and pharmacological agents that prevent expression of antibiotic resistance. The rise in multiresistant bacteria harboring AAC(6')-Ib has seriously limited the effectiveness of amikacin and other aminoglycosides. We have recently shown that recombinant plasmids coding for external guide sequences (EGS), short antisense oligoribonucleotides (ORN) that elicit RNase P-mediated cleavage of a target mRNA, induce inhibition of expression of aac(6')-Ib and concomitantly induce a significant decrease in the levels of resistance to amikacin. However, since ORN are rapidly degraded by nucleases, development of a viable RNase P-based antisense technology requires the design of nuclease-resistant RNA analog EGSs. We have assayed a variety of ORN analogs of which selected LNA/DNA co-oligomers elicited RNase P-mediated cleavage of mRNA in vitro. Although we found an ideal configuration of LNA/DNA residues, there seems not to be a correlation between number of LNA substitutions and level of activity. Exogenous administration of as low as 50 nM of an LNA/DNA co-oligomer to the hyperpermeable E. coli AS19 harboring the aac(6')-Ib inhibited growth in the presence of amikacin. Our experiments strongly suggest an RNase P-mediated mechanism in the observed antisense effect.
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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.