ArticlePLoS pathogens2020
Evolving MRSA: High-level β-lactam resistance in Staphylococcus aureus is associated with RNA Polymerase alterations and fine tuning of gene expression.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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
57 citing papers in PubMed.
- Collateral sensitivity-harnessing microbial vulnerabilities as a solution to antimicrobial resistance.Molecular biology reports · 2026Review
- An Achilles' heel for methicillin-resistantAntimicrobial agents and chemotherapy · 2026Review
- Mutations in RNA polymerase that drive the emergence of antibiotic resistance.Current opinion in microbiology · 2026Review
- Statin-induced lipid carrier stress reveals a conserved vulnerability in β-lactam-resistant Gram-positive bacteria.Nature communications · 2026Article
- Epistasis and co-adaptation in bacterial genome evolution.Nature reviews. Genetics · 2026Review
- Resistance potentiators: Evolutionary catalysts of antibiotic resistance.PLoS biology · 2026Article
- Genotypic and phenotypic features of MRSA with an incomplete hemolysis phenotype in a tertiary teaching hospital in China.BMC microbiology · 2026Article
- Prevalence of Antimicrobial-Resistant Bacterial Pathogens Among Livestock in Subtropical Environments.Antibiotics (Basel, Switzerland) · 2026Article
- Methicillin-resistantAntimicrobial agents and chemotherapy · 2026Article
- Trends, Seasonality, and the Impact of COVID-19 on ClinicalAntibiotics (Basel, Switzerland) · 2026Article
- BeyondAntimicrobial agents and chemotherapy · 2026Article
- Mutation of lipoprotein processing pathway geneAntimicrobial agents and chemotherapy · 2026Article
- Expression ofmBio · 2025Article
- Article
- Evolution of beta-lactam resistance causes fitness reductions and several cases of collateral sensitivities in the human pathogenAntimicrobial agents and chemotherapy · 2025Article
- Staphylococcus aureus COL: An Atypical Model Strain of MRSA That Exhibits Slow Growth and Antibiotic Tolerance due to a Mutation in PRPP Synthetase.Molecular microbiology · 2025Article
- Review
- The impact of bacterial purine metabolism on antibiotic efficacy.npj antimicrobials and resistance · 2025Review
- Article
- A Mechanistic Insight into the Anti-Staphylococcal Mode of Action of (+)-Usnic Acid and Its Synergy with Norfloxacin Against Methicillin-ResistantBiomolecules · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
Most clinical MRSA (methicillin-resistant S. aureus) isolates exhibit low-level β-lactam resistance (oxacillin MIC 2-4 μg/ml) due to the acquisition of a novel penicillin binding protein (PBP2A), encoded by mecA. However, strains can evolve high-level resistance (oxacillin MIC ≥256 μg/ml) by an unknown mechanism. Here we have developed a robust system to explore the basis of the evolution of high-level resistance by inserting mecA into the chromosome of the methicillin-sensitive S. aureus SH1000. Low-level mecA-dependent oxacillin resistance was associated with increased expression of anaerobic respiratory and fermentative genes. High-level resistant derivatives had acquired mutations in either rpoB (RNA polymerase subunit β) or rpoC (RNA polymerase subunit β') and these mutations were shown to be responsible for the observed resistance phenotype. Analysis of rpoB and rpoC mutants revealed decreased growth rates in the absence of antibiotic, and alterations to, transcription elongation. The rpoB and rpoC mutations resulted in decreased expression to parental levels, of anaerobic respiratory and fermentative genes and specific upregulation of 11 genes including mecA. There was however no direct correlation between resistance and the amount of PBP2A. A mutational analysis of the differentially expressed genes revealed that a member of the S. aureus Type VII secretion system is required for high level resistance. Interestingly, the genomes of two of the high level resistant evolved strains also contained missense mutations in this same locus. Finally, the set of genetically matched strains revealed that high level antibiotic resistance does not incur a significant fitness cost during pathogenesis. Our analysis demonstrates the complex interplay between antibiotic resistance mechanisms and core cell physiology, providing new insight into how such important resistance properties evolve.
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.