ArticleAntimicrobial agents and chemotherapy2004
Ketolide antimicrobial activity persists after disruption of interactions with domain II of 23S rRNA.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- Novel Macrolide Antibiotic Nafithromycin for Tackling Emerging Resistance in Respiratory Pathogens Encountered in India.Current microbiology · 2025Review
- Molecular detection of antimicrobial resistance in livestock mycoplasmas: current status and future prospects.Frontiers in veterinary science · 2025Review
- Recoding of Nonsense Mutation as a Pharmacological Strategy.Biomedicines · 2023Review
- Nonsense suppression therapies in human genetic diseases.Cellular and molecular life sciences : CMLS · 2021Review
- Antimicrobial Resistance inMicrobiology spectrum · 2018Review
- Methylation of 23S rRNA nucleotide G748 by RlmAII methyltransferase renders Streptococcus pneumoniae telithromycin susceptible.Antimicrobial agents and chemotherapy · 2013Article
- Inhibition of protein synthesis on the ribosome by tildipirosin compared with other veterinary macrolides.Antimicrobial agents and chemotherapy · 2012Article
- Investigating the entire course of telithromycin binding to Escherichia coli ribosomes.Nucleic acids research · 2012Article
- The chemistry of peptidyltransferase center-targeted antibiotics: enzymatic resistance and approaches to countering resistance.ACS chemical biology · 2012Review
- Binding and action of CEM-101, a new fluoroketolide antibiotic that inhibits protein synthesis.Antimicrobial agents and chemotherapy · 2010Article
- Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Macrolide- and telithromycin-resistant Streptococcus pyogenes, Belgium, 1999-2003.Emerging infectious diseases · 2005Article
- Pharmacodynamic activity of telithromycin at simulated clinically achievable free-drug concentrations in serum and epithelial lining fluid against efflux (mefE)-producing macrolide-resistant Streptococcus pneumoniae for which telithromycin MICs vary.Antimicrobial agents and chemotherapy · 2005Article
- 23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A-->G.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ketolides are the latest derivatives developed from the macrolide erythromycin to improve antimicrobial activity. All macrolides and ketolides bind to the 50S ribosomal subunit, where they come into contact with adenosine 2058 (A2058) within domain V of the 23S rRNA and block protein synthesis. An additional interaction at nucleotide A752 in the rRNA domain II is made via the synthetic carbamate-alkyl-aryl substituent in the ketolides HMR3647 (telithromycin) and HMR3004, and this interaction contributes to their improved activities. Only a few macrolides, including tylosin, come into contact with domain II of the rRNA and do so via interactions with nucleotides G748 and A752. We have disrupted these macrolide-ketolide interaction sites in the rRNA to assess their relative importance for binding. Base substitutions at A752 were shown to confer low levels of resistance to telithromycin but not to HMR3004, while deletion of A752 confers low levels of resistance to both ketolides. Mutations at position 748 confer no resistance. Substitution of guanine at A2058 gives rise to the MLS(B) (macrolide, lincosamide, and streptogramin B) phenotype, which confers resistance to all the drugs. However, resistance to ketolides was abolished when the mutation at position 2058 was combined with a mutation in domain II of the same rRNA. In contrast, the same dual mutations in rRNAs conferred enhanced resistance to tylosin. Our results show that the domain II interactions of telithromycin and HMR3004 differ from each other and from those of tylosin. The data provide no indication that mutations within domain II, either alone or in combination with an A2058 mutation, can confer significant levels of telithromycin resistance.
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