ArticleProceedings of the National Academy of Sciences of the United States of America2005
Deleterious mutations in small subunit ribosomal RNA identify functional sites and potential targets for antibiotics.
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 43 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 83 citations in OpenAlex.
- How Medically Important Antimicrobials Bind to the 30S Ribosomal Subunit in a Bacterial Pathogen.Biochemistry · 2026Article
- Genomic Analysis of Doxycycline Resistance-Associated 16S rRNA Mutations in Treponema pallidum Subspecies pallidum.Emerging infectious diseases · 2026Article
- Genome-wide screening of antibiotic survival genes in Escherichia coli MG1655.BMC microbiology · 2026Article
- Ribosome Pool Engineering Increases Protein Biosynthesis Yields.ACS central science · 2024Article
- Variable Region Sequences Influence 16S rRNA Performance.Microbiology spectrum · 2023Article
- Community science designed ribosomes with beneficial phenotypes.Nature communications · 2023Article
- Structural analysis of mitochondrial rRNA gene variants identified in patients with deafness.Frontiers in physiology · 2023Article
- Computationally-guided design and selection of high performing ribosomal active site mutants.Nucleic acids research · 2022Article
- Overview on Strategies and Assays for Antibiotic Discovery.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Comparative Analysis of anti-Shine- Dalgarno Function inFrontiers in molecular biosciences · 2021Article
- Molecular Phylogenetic Analysis ofInternational journal of microbiology · 2020Article
- Occurrence of randomly recombined functional 16S rRNA genes in Thermus thermophilus suggests genetic interoperability and promiscuity of bacterial 16S rRNAs.Scientific reports · 2019Article
- Functional metagenomic approach to identify overlooked antibiotic resistance mutations in bacterial rRNA.Scientific reports · 2018Article
- PointFinder: a novel web tool for WGS-based detection of antimicrobial resistance associated with chromosomal point mutations in bacterial pathogens.The Journal of antimicrobial chemotherapy · 2017Article
- Random pseuoduridylation in vivo reveals critical region of Escherichia coli 23S rRNA for ribosome assembly.Nucleic acids research · 2017Article
- How Changes in Anti-SD Sequences Would Affect SD Sequences inG3 (Bethesda, Md.) · 2017Article
- One step engineering of the small-subunit ribosomal RNA using CRISPR/Cas9.Scientific reports · 2016Article
- Resistance mutations generate divergent antibiotic susceptibility profiles against translation inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Efficient Synthesis and Antibacterial Evaluation of (±)-Yanglingmycin and Its Analogues.Molecules (Basel, Switzerland) · 2016Article
- Assembly constraints drive co-evolution among ribosomal constituents.Nucleic acids research · 2015Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Many clinically useful antibiotics interfere with protein synthesis in bacterial pathogens by inhibiting ribosome function. The sites of action of known drugs are limited in number, are composed primarily of ribosomal RNA (rRNA), and coincide with functionally critical centers of the ribosome. Nucleotide alterations within such sites are often deleterious. To identify functional sites and potential sites of antibiotic action in the ribosome, we prepared a random mutant library of rRNA genes and selected dominant mutations in 16S rRNA that interfere with cell growth. Fifty-three 16S rRNA positions were identified whose mutation inhibits protein synthesis. Mutations were ranked according to the severity of the phenotype, and the detrimental effect of several mutations on translation was verified in a specialized ribosome system. Analysis of the polysome profiles of mutants suggests that the majority of the mutations directly interfered with ribosome function, whereas a smaller fraction of mutations affected assembly of the small ribosomal subunit. Twelve of the identified mutations mapped to sites targeted by known antibiotics, confirming that deleterious mutations can be used to identify antibiotic targets. About half of the mutations coincided with known functional sites in the ribosome, whereas the rest of the mutations affected ribosomal sites with less clear functional significance. Four clusters of deleterious mutations in otherwise unremarkable ribosomal sites were identified, suggesting their functional importance and potential as antibiotic targets.
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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.