Metabolic constraints on the evolution of antibiotic resistance
Abstract Despite our continuous improvement in understanding antibiotic resistance, the interplay between natural selection of resistance mutations and the environment remains unclear. To investigate the role of bacterial metabolism in constraining the evolution of antibiotic resistance, we evolved...
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| Format: | Article |
| Language: | English |
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Springer Nature
2017-03-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20167028 |
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| _version_ | 1841544126832574464 |
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| author | Mattia Zampieri Tim Enke Victor Chubukov Vito Ricci Laura Piddock Uwe Sauer |
| author_facet | Mattia Zampieri Tim Enke Victor Chubukov Vito Ricci Laura Piddock Uwe Sauer |
| author_sort | Mattia Zampieri |
| collection | DOAJ |
| description | Abstract Despite our continuous improvement in understanding antibiotic resistance, the interplay between natural selection of resistance mutations and the environment remains unclear. To investigate the role of bacterial metabolism in constraining the evolution of antibiotic resistance, we evolved Escherichia coli growing on glycolytic or gluconeogenic carbon sources to the selective pressure of three different antibiotics. Profiling more than 500 intracellular and extracellular putative metabolites in 190 evolved populations revealed that carbon and energy metabolism strongly constrained the evolutionary trajectories, both in terms of speed and mode of resistance acquisition. To interpret and explore the space of metabolome changes, we developed a novel constraint‐based modeling approach using the concept of shadow prices. This analysis, together with genome resequencing of resistant populations, identified condition‐dependent compensatory mechanisms of antibiotic resistance, such as the shift from respiratory to fermentative metabolism of glucose upon overexpression of efflux pumps. Moreover, metabolome‐based predictions revealed emerging weaknesses in resistant strains, such as the hypersensitivity to fosfomycin of ampicillin‐resistant strains. Overall, resolving metabolic adaptation throughout antibiotic‐driven evolutionary trajectories opens new perspectives in the fight against emerging antibiotic resistance. |
| format | Article |
| id | doaj-art-4688e89cb6064401ad35704f1157aa8e |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2017-03-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-4688e89cb6064401ad35704f1157aa8e2025-01-12T12:45:36ZengSpringer NatureMolecular Systems Biology1744-42922017-03-0113311410.15252/msb.20167028Metabolic constraints on the evolution of antibiotic resistanceMattia Zampieri0Tim Enke1Victor Chubukov2Vito Ricci3Laura Piddock4Uwe Sauer5Institute of Molecular Systems Biology, ETH ZürichInstitute of Molecular Systems Biology, ETH ZürichInstitute of Molecular Systems Biology, ETH ZürichInstitute of Microbiology and Infection, University of BirminghamInstitute of Microbiology and Infection, University of BirminghamInstitute of Molecular Systems Biology, ETH ZürichAbstract Despite our continuous improvement in understanding antibiotic resistance, the interplay between natural selection of resistance mutations and the environment remains unclear. To investigate the role of bacterial metabolism in constraining the evolution of antibiotic resistance, we evolved Escherichia coli growing on glycolytic or gluconeogenic carbon sources to the selective pressure of three different antibiotics. Profiling more than 500 intracellular and extracellular putative metabolites in 190 evolved populations revealed that carbon and energy metabolism strongly constrained the evolutionary trajectories, both in terms of speed and mode of resistance acquisition. To interpret and explore the space of metabolome changes, we developed a novel constraint‐based modeling approach using the concept of shadow prices. This analysis, together with genome resequencing of resistant populations, identified condition‐dependent compensatory mechanisms of antibiotic resistance, such as the shift from respiratory to fermentative metabolism of glucose upon overexpression of efflux pumps. Moreover, metabolome‐based predictions revealed emerging weaknesses in resistant strains, such as the hypersensitivity to fosfomycin of ampicillin‐resistant strains. Overall, resolving metabolic adaptation throughout antibiotic‐driven evolutionary trajectories opens new perspectives in the fight against emerging antibiotic resistance.https://doi.org/10.15252/msb.20167028antibiotic resistanceconstraint‐based modelingefflux pumpevolutionmetabolism |
| spellingShingle | Mattia Zampieri Tim Enke Victor Chubukov Vito Ricci Laura Piddock Uwe Sauer Metabolic constraints on the evolution of antibiotic resistance Molecular Systems Biology antibiotic resistance constraint‐based modeling efflux pump evolution metabolism |
| title | Metabolic constraints on the evolution of antibiotic resistance |
| title_full | Metabolic constraints on the evolution of antibiotic resistance |
| title_fullStr | Metabolic constraints on the evolution of antibiotic resistance |
| title_full_unstemmed | Metabolic constraints on the evolution of antibiotic resistance |
| title_short | Metabolic constraints on the evolution of antibiotic resistance |
| title_sort | metabolic constraints on the evolution of antibiotic resistance |
| topic | antibiotic resistance constraint‐based modeling efflux pump evolution metabolism |
| url | https://doi.org/10.15252/msb.20167028 |
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