ArticleProceedings of the National Academy of Sciences of the United States of America2005
23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A-->G.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 80 citations in OpenAlex.
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- Resurgence ofEuro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2024Article
- Emergence and Mechanism of Resistance of Tulathromycin AgainstFrontiers in veterinary science · 2022Article
- Expanding the Scope of Protein Synthesis Using Modified Ribosomes.Journal of the American Chemical Society · 2019Article
- Mycobacterium smegmatis PafBC is involved in regulation of DNA damage response.Scientific reports · 2017Article
- The macrolide antibiotic renaissance.British journal of pharmacology · 2017Review
- New Real-Time PCR Assays for Detection of Inducible and Acquired Clarithromycin Resistance in the Mycobacterium abscessus Group.Journal of clinical microbiology · 2015Article
- Nuclear modifier MTO2 modulates the aminoglycoside-sensitivity of mitochondrial 15S rRNA C1477G mutation in Saccharomyces cerevisiae.PloS one · 2013Article
- Investigating the entire course of telithromycin binding to Escherichia coli ribosomes.Nucleic acids research · 2012Article
- Phylogenetic sequence variations in bacterial rRNA affect species-specific susceptibility to drugs targeting protein synthesis.Antimicrobial agents and chemotherapy · 2011Article
- Trends towards lower antimicrobial susceptibility and characterization of acquired resistance among clinical isolates of Brachyspira hyodysenteriae in Spain.Antimicrobial agents and chemotherapy · 2011Article
- The origin of a derived superkingdom: how a gram-positive bacterium crossed the desert to become an archaeon.Biology direct · 2011Article
- The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Genetic analysis of interactions with eukaryotic rRNA identify the mitoribosome as target in aminoglycoside ototoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Macrolide myths.Current opinion in microbiology · 2008Review
- Novel mutation in 23S rRNA that confers low-level resistance to clarithromycin in Helicobacter pylori.Antimicrobial agents and chemotherapy · 2008Article
- Mutation from guanine to adenine in 25S rRNA at the position equivalent to E. coli A2058 does not confer erythromycin sensitivity in Sacchromyces cerevisae.RNA (New York, N.Y.) · 2008Article
- Eukaryotic ribosomal RNA determinants of aminoglycoside resistance and their role in translational fidelity.RNA (New York, N.Y.) · 2008Article
- Frequency of development and associated physiological cost of azithromycin resistance in Chlamydia psittaci 6BC and C. trachomatis L2.Antimicrobial agents and chemotherapy · 2007Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The 23S rRNA A2058G alteration mediates macrolide, lincosamide, and streptogramin B resistance in the bacterial domain and determines the selectivity of macrolide antibiotics for eubacterial ribosomes, as opposed to eukaryotic ribosomes. However, this mutation is associated with a disparate resistance phenotype: It confers high-level resistance to ketolides in mycobacteria but only marginally affects ketolide susceptibility in streptococci. We used site-directed mutagenesis of nucleotides within domain V of 23S rRNA to study the molecular basis for this disparity. We show that mutational alteration of the polymorphic 2057-2611 base pair from A-U to G-C in isogenic mutants of Mycobacterium smegmatis significantly affects susceptibility to ketolides but does not influence susceptibility to other macrolide antibiotics. In addition, we provide evidence that the 2057-2611 polymorphism determines the fitness cost of the 23S rRNA A2058G resistance mutation. Supported by structural analysis, our results indicate that polymorphic nucleotides mediate the disparate phenotype of genotypically identical resistance mutations and provide an explanation for the large species differences in the epidemiology of defined drug resistance mutations.
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