ArticleRNA (New York, N.Y.)2016
Nonmutational compensation of the fitness cost of antibiotic resistance in mycobacteria by overexpression of tlyA rRNA methylase.
Article in RNA (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 48 citations in OpenAlex.
- Distant ribose 2'-O-methylation of 23S rRNA helix 69 pre-orders the capreomycin drug binding pocket at the ribosome subunit interface.Nucleic acids research · 2025Article
- Article
- Discordance Between Phenotypic and WGS-Based Drug Susceptibility Testing Results for Some Anti-Tuberculosis Drugs: A Snapshot Study of PairedInfection and drug resistance · 2024Article
- Translating eco-evolutionary biology into therapy to tackle antibiotic resistance.Nature reviews. Microbiology · 2023Review
- What are the missing pieces needed to stop antibiotic resistance?Microbial biotechnology · 2023Review
- Disrupting the ArcA Regulatory Network Amplifies the Fitness Cost of Tetracycline Resistance in Escherichia coli.mSystems · 2023Article
- Evolution of Habitat-Dependent Antibiotic Resistance in Pseudomonas aeruginosa.Microbiology spectrum · 2022Article
- 50S subunit recognition and modification by theProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Tuberactinomycin antibiotics: Biosynthesis, anti-mycobacterial action, and mechanisms of resistance.Frontiers in microbiology · 2022Review
- Rapid Identification of Drug-Resistant Tuberculosis Genes Using Direct PCR Amplification and Oxford Nanopore Technology Sequencing.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2022Article
- The evolving biology ofFrontiers in cellular and infection microbiology · 2022Review
- Evolutionary Pathways and Trajectories in Antibiotic Resistance.Clinical microbiology reviews · 2021Article
- Climatic Alterations Influence Bacterial Growth, Biofilm Production and Antimicrobial Resistance Profiles inAntibiotics (Basel, Switzerland) · 2021Article
- Genome-Based Analyses of Fitness Effects and Compensatory Changes Associated with Acquisition ofAntibiotics (Basel, Switzerland) · 2021Article
- Antibiotic resistance: Time of synthesis in a post-genomic age.Computational and structural biotechnology journal · 2021Review
- METTL15 interacts with the assembly intermediate of murine mitochondrial small ribosomal subunit to form m4C840 12S rRNA residue.Nucleic acids research · 2020Article
- Using genomics to understand the origin and dispersion of multidrug and extensively drug resistant tuberculosis in Portugal.Scientific reports · 2020Article
- Article
- Translational control of antibiotic resistance.Open biology · 2019Review
- Whole-Genome Sequencing for Drug Resistance Profile Prediction inAntimicrobial agents and chemotherapy · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several studies over the last few decades have shown that antibiotic resistance mechanisms frequently confer a fitness cost and that these costs can be genetically ameliorated by intra- or extragenic second-site mutations, often without loss of resistance. Another, much less studied potential mechanism by which the fitness cost of antibiotic resistance could be reduced is via a regulatory response where the deleterious effect of the resistance mechanism is lowered by a physiological alteration that buffers the mutational effect. In mycobacteria, resistance to the clinically used tuberactinomycin antibiotic capreomycin involves loss-of-function mutations in rRNA methylase TlyA or point mutations in 16S rRNA (in particular the A1408G mutation). Both of these alterations result in resistance by reducing drug binding to the ribosome. Here we show that alterations of tlyA gene expression affect both antibiotic drug susceptibility and fitness cost of drug resistance. In particular, we demonstrate that the common resistance mutation A1408G is accompanied by a physiological change that involves increased expression of the tlyA gene. This gene encodes an enzyme that methylates neighboring 16S rRNA position C1409, and as a result of increased TlyA expression the fitness cost of the A1408G mutation is significantly reduced. Our findings suggest that in mycobacteria, a nonmutational mechanism (i.e., gene regulatory) can restore fitness to genetically resistant bacteria. Our results also point to a new and clinically relevant treatment strategy to combat evolution of resistance in multidrug-resistant tuberculosis. Thus, by utilizing antagonistic antibiotic interactions, resistance evolution could be reduced.
Indexed as
Identifiers
What OpenQuestion holds
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.