ArticlePLoS pathogens2010
Novel riboswitch ligand analogs as selective inhibitors of guanine-related metabolic pathways.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 167 citations in OpenAlex.
- D-alanine aminotransferase (Dat) promotesbioRxiv : the preprint server for biology · 2026Article
- Identification of bacterial key genes and therapeutic targets in hypertensive patients with type 2 diabetes through bioinformatics analysis.Scientific reports · 2026Article
- Engineering oxypurinol-responsive riboswitches based on bacterial xanthine aptamers for gene expression control in mammalian cell culture.Nucleic acids research · 2025Article
- Article
- The current riboswitch landscape inMicrobiology (Reading, England) · 2024Review
- Opportunities for Riboswitch Inhibition by Targeting Co-Transcriptional RNA Folding Events.International journal of molecular sciences · 2024Review
- A sensitive and scalable fluorescence anisotropy single stranded RNA targeting approach for monitoring riboswitch conformational states.Nucleic acids research · 2024Article
- Regulation of bacterial gene expression by non-coding RNA: It is all about time!Cell chemical biology · 2024Review
- Targeting FMN, TPP, SAM-I, and glmS Riboswitches with Chimeric Antisense Oligonucleotides for Completely Rational Antibacterial Drug Development.Antibiotics (Basel, Switzerland) · 2023Review
- Rationally Designed Pyrimidine Compounds: Promising Novel Antibiotics for the Treatment ofAntibiotics (Basel, Switzerland) · 2023Article
- Mechanism of Ligand Discrimination by theJournal of chemical information and modeling · 2023Article
- Targeting Riboswitches with Beta-Axial-Substituted Cobalamins.ACS chemical biology · 2023Article
- Effective Treatment ofViruses · 2023Article
- Discovering riboswitches: the past and the future.Trends in biochemical sciences · 2023Review
- Characterization of the glmS Ribozymes from Listeria Monocytogenes and Clostridium Difficile.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- X-Ray Crystallography to Study Conformational Changes in a TPP Riboswitch.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Developing New Tools to Fight Human Pathogens: A Journey through the Advances in RNA Technologies.Microorganisms · 2022Review
- A Riboswitch-Driven Era of New Antibacterials.Antibiotics (Basel, Switzerland) · 2022Review
- Inactivation of the riboswitch-controlled GMP synthase GuaA inRNA biology · 2021Article
- Quantitative mapping of mRNA 3' ends in Pseudomonas aeruginosa reveals a pervasive role for premature 3' end formation in response to azithromycin.PLoS genetics · 2021Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Riboswitches are regulatory elements modulating gene expression in response to specific metabolite binding. It has been recently reported that riboswitch agonists may exhibit antimicrobial properties by binding to the riboswitch domain. Guanine riboswitches are involved in the regulation of transport and biosynthesis of purine metabolites, which are critical for the nucleotides cellular pool. Upon guanine binding, these riboswitches stabilize a 5'-untranslated mRNA structure that causes transcription attenuation of the downstream open reading frame. In principle, any agonistic compound targeting a guanine riboswitch could cause gene repression even when the cell is starved for guanine. Antibiotics binding to riboswitches provide novel antimicrobial compounds that can be rationally designed from riboswitch crystal structures. Using this, we have identified a pyrimidine compound (PC1) binding guanine riboswitches that shows bactericidal activity against a subgroup of bacterial species including well-known nosocomial pathogens. This selective bacterial killing is only achieved when guaA, a gene coding for a GMP synthetase, is under the control of the riboswitch. Among the bacterial strains tested, several clinical strains exhibiting multiple drug resistance were inhibited suggesting that PC1 targets a different metabolic pathway. As a proof of principle, we have used a mouse model to show a direct correlation between the administration of PC1 and the reduction of Staphylococcus aureus infection in mammary glands. This work establishes the possibility of using existing structural knowledge to design novel guanine riboswitch-targeting antibiotics as powerful and selective antimicrobial compounds. Particularly, the finding of this new guanine riboswitch target is crucial as community-acquired bacterial infections have recently started to emerge.
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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.