ArticleProceedings. Biological sciences2016
The genomic basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa.
Article in Proceedings. Biological sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Simulating the host niche: balancing complexity and control in the experimental evolution of antibiotic resistance and pathoadaptation.Microbiology (Reading, England) · 2026Review
- Novel dual regulatory roles of RpoA in quorum sensing regulation and social behavior switching inmBio · 2026Article
- Evolution and evolvability of rifampicin resistance across the bacterial tree of life.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Effect of compensatory evolution in the emergence and transmission of rifampicin-resistant Mycobacterium tuberculosis in Cape Town, South Africa: a genomic epidemiology study.The Lancet. Microbe · 2023Article
- The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot.Nature communications · 2023Article
- A rise in the frequency ofFrontiers in cellular and infection microbiology · 2023Article
- The balance between antibiotic resistance and fitness/virulence inFrontiers in microbiology · 2023Review
- Mutations compensating for the fitness cost of rifampicin resistance in Escherichia coli exert pleiotropic effect on RNA polymerase catalysis.Nucleic acids research · 2022Article
- Article
- Biofilm Maintenance as an Active Process: Evidence that Biofilms Work Hard to Stay Put.Journal of bacteriology · 2022Review
- Revisiting Antibiotic Resistance: Mechanistic Foundations to Evolutionary Outlook.Antibiotics (Basel, Switzerland) · 2021Review
- Adaptation and compensation in a bacterial gene regulatory network evolving under antibiotic selection.eLife · 2021Article
- Fitness benefits to bacteria of carrying prophages and prophage-encoded antibiotic-resistance genes peak in different environments.Evolution; international journal of organic evolution · 2021Article
- Extreme Antagonism Arising from Gene-Environment Interactions.Biophysical journal · 2020Article
- Rapid decline of bacterial drug-resistance in an antibiotic-free environment through phenotypic reversion.eLife · 2019Article
- Article
- Experimental Design, Population Dynamics, and Diversity in Microbial Experimental Evolution.Microbiology and molecular biology reviews : MMBR · 2018Review
- Article
- Epistasis and the Evolution of Antimicrobial Resistance.Frontiers in microbiology · 2017Review
- Survival and Evolution of a Large Multidrug Resistance Plasmid in New Clinical Bacterial Hosts.Molecular biology and evolution · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Antibiotic resistance carries a fitness cost that must be overcome in order for resistance to persist over the long term. Compensatory mutations that recover the functional defects associated with resistance mutations have been argued to play a key role in overcoming the cost of resistance, but compensatory mutations are expected to be rare relative to generally beneficial mutations that increase fitness, irrespective of antibiotic resistance. Given this asymmetry, population genetics theory predicts that populations should adapt by compensatory mutations when the cost of resistance is large, whereas generally beneficial mutations should drive adaptation when the cost of resistance is small. We tested this prediction by determining the genomic mechanisms underpinning adaptation to antibiotic-free conditions in populations of the pathogenic bacterium Pseudomonas aeruginosa that carry costly antibiotic resistance mutations. Whole-genome sequencing revealed that populations founded by high-cost rifampicin-resistant mutants adapted via compensatory mutations in three genes of the RNA polymerase core enzyme, whereas populations founded by low-cost mutants adapted by generally beneficial mutations, predominantly in the quorum-sensing transcriptional regulator gene lasR. Even though the importance of compensatory evolution in maintaining resistance has been widely recognized, our study shows that the roles of general adaptation in maintaining resistance should not be underestimated and highlights the need to understand how selection at other sites in the genome influences the dynamics of resistance alleles in clinical settings.
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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.