Efflux pump activity potentiates the evolution of antibiotic resistance across S. aureus isolates
| Autor: | Bernadette C. Young, Andrei Papkou, R. Craig MacLean, Natalia Kapel, Jessica Hedge |
|---|---|
| Přispěvatelé: | University of Zurich, Papkou, Andrei, MacLean, R Craig |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Antibiotics General Physics and Astronomy 02 engineering and technology Drug resistance Antimicrobial resistance medicine.disease_cause Ciprofloxacin Bacterial genetics lcsh:Science Phylogeny Experimental evolution Multidisciplinary Drug Resistance Microbial 021001 nanoscience & nanotechnology 3100 General Physics and Astronomy Staphylococcus aureus 590 Animals (Zoology) Efflux 0210 nano-technology medicine.drug medicine.drug_class Science 1600 General Chemistry Genetics and Molecular Biology Biology Article General Biochemistry Genetics and Molecular Biology Microbiology Evolution Molecular 10127 Institute of Evolutionary Biology and Environmental Studies 03 medical and health sciences Antibiotic resistance Bacterial Proteins 1300 General Biochemistry Genetics and Molecular Biology medicine Bacterial genomics Gene Expression Regulation Bacterial General Chemistry 030104 developmental biology General Biochemistry Mutation 570 Life sciences biology lcsh:Q Transcriptome Genome Bacterial |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-17735-y |
| Popis: | The rise of antibiotic resistance in many bacterial pathogens has been driven by the spread of a few successful strains, suggesting that some bacteria are genetically pre-disposed to evolving resistance. Here, we test this hypothesis by challenging a diverse set of 222 isolates of Staphylococcus aureus with the antibiotic ciprofloxacin in a large-scale evolution experiment. We find that a single efflux pump, norA, causes widespread variation in evolvability across isolates. Elevated norA expression potentiates evolution by increasing the fitness benefit provided by DNA topoisomerase mutations under ciprofloxacin treatment. Amplification of norA provides a further mechanism of rapid evolution in isolates from the CC398 lineage. Crucially, chemical inhibition of NorA effectively prevents the evolution of resistance in all isolates. Our study shows that pre-existing genetic diversity plays a key role in shaping resistance evolution, and it may be possible to predict which strains are likely to evolve resistance and to optimize inhibitor use to prevent this outcome. Some bacterial lineages appear to be pre-disposed to evolving antibiotic resistance. Here, the authors show that differential expression of an efflux pump causes widespread variation in evolvability across Staphylococcus aureus isolates, and chemical inhibition of the pump prevents resistance evolution. |
| Databáze: | OpenAIRE |
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