The population genetics of collateral resistance and sensitivity
Resistance mutations against one drug can elicit collateral sensitivity against other drugs. Multi-drug treatments exploiting such trade-offs can help slow down the evolution of resistance. However, if mutations with diverse collateral effects are available, a treated population may evolve either co...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/73250 |
| _version_ | 1811199873264910336 |
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| author | Sarah M Ardell Sergey Kryazhimskiy |
| author_facet | Sarah M Ardell Sergey Kryazhimskiy |
| author_sort | Sarah M Ardell |
| collection | DOAJ |
| description | Resistance mutations against one drug can elicit collateral sensitivity against other drugs. Multi-drug treatments exploiting such trade-offs can help slow down the evolution of resistance. However, if mutations with diverse collateral effects are available, a treated population may evolve either collateral sensitivity or collateral resistance. How to design treatments robust to such uncertainty is unclear. We show that many resistance mutations in Escherichia coli against various antibiotics indeed have diverse collateral effects. We propose to characterize such diversity with a joint distribution of fitness effects (JDFE) and develop a theory for describing and predicting collateral evolution based on simple statistics of the JDFE. We show how to robustly rank drug pairs to minimize the risk of collateral resistance and how to estimate JDFEs. In addition to practical applications, these results have implications for our understanding of evolution in variable environments. |
| first_indexed | 2024-04-12T01:54:49Z |
| format | Article |
| id | doaj.art-7309f0ad89504e10b1d990083a00280f |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:54:49Z |
| publishDate | 2021-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7309f0ad89504e10b1d990083a00280f2022-12-22T03:52:49ZengeLife Sciences Publications LtdeLife2050-084X2021-12-011010.7554/eLife.73250The population genetics of collateral resistance and sensitivitySarah M Ardell0https://orcid.org/0000-0001-6665-2739Sergey Kryazhimskiy1https://orcid.org/0000-0001-9128-8705Division of Biological Sciences, University of California, San Diego, La Jolla, United StatesDivision of Biological Sciences, University of California, San Diego, La Jolla, United StatesResistance mutations against one drug can elicit collateral sensitivity against other drugs. Multi-drug treatments exploiting such trade-offs can help slow down the evolution of resistance. However, if mutations with diverse collateral effects are available, a treated population may evolve either collateral sensitivity or collateral resistance. How to design treatments robust to such uncertainty is unclear. We show that many resistance mutations in Escherichia coli against various antibiotics indeed have diverse collateral effects. We propose to characterize such diversity with a joint distribution of fitness effects (JDFE) and develop a theory for describing and predicting collateral evolution based on simple statistics of the JDFE. We show how to robustly rank drug pairs to minimize the risk of collateral resistance and how to estimate JDFEs. In addition to practical applications, these results have implications for our understanding of evolution in variable environments.https://elifesciences.org/articles/73250pleiotropytrade-offsjoint distribution of fitness effects |
| spellingShingle | Sarah M Ardell Sergey Kryazhimskiy The population genetics of collateral resistance and sensitivity eLife pleiotropy trade-offs joint distribution of fitness effects |
| title | The population genetics of collateral resistance and sensitivity |
| title_full | The population genetics of collateral resistance and sensitivity |
| title_fullStr | The population genetics of collateral resistance and sensitivity |
| title_full_unstemmed | The population genetics of collateral resistance and sensitivity |
| title_short | The population genetics of collateral resistance and sensitivity |
| title_sort | population genetics of collateral resistance and sensitivity |
| topic | pleiotropy trade-offs joint distribution of fitness effects |
| url | https://elifesciences.org/articles/73250 |
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