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Collateral Sensitivity Interactions between Antibiotics Depend on Local Abiotic Conditions
Mutations conferring resistance to one antibiotic can increase (cross-resistance) or decrease (collateral sensitivity) resistance to others. Antibiotic combinations displaying collateral sensitivity could be used in treatments that slow resistance evolution. However, lab-to-clinic translation requir...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631318/ https://www.ncbi.nlm.nih.gov/pubmed/34846167 http://dx.doi.org/10.1128/mSystems.01055-21 |
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author | Allen, Richard C. Pfrunder-Cardozo, Katia R. Hall, Alex R. |
author_facet | Allen, Richard C. Pfrunder-Cardozo, Katia R. Hall, Alex R. |
author_sort | Allen, Richard C. |
collection | PubMed |
description | Mutations conferring resistance to one antibiotic can increase (cross-resistance) or decrease (collateral sensitivity) resistance to others. Antibiotic combinations displaying collateral sensitivity could be used in treatments that slow resistance evolution. However, lab-to-clinic translation requires understanding whether collateral effects are robust across different environmental conditions. Here, we isolated and characterized resistant mutants of Escherichia coli using five antibiotics, before measuring collateral effects on resistance to other paired antibiotics. During both isolation and phenotyping, we varied conditions in ways relevant in nature (pH, temperature, and bile). This revealed that local abiotic conditions modified expression of resistance against both the antibiotic used during isolation and other antibiotics. Consequently, local conditions influenced collateral sensitivity in two ways: by favoring different sets of mutants (with different collateral sensitivities) and by modifying expression of collateral effects for individual mutants. These results place collateral sensitivity in the context of environmental variation, with important implications for translation to real-world applications. IMPORTANCE When bacteria become resistant to an antibiotic, the genetic changes involved sometimes increase (cross-resistance) or decrease (collateral sensitivity) their resistance to other antibiotics. Antibiotic combinations showing repeatable collateral sensitivity could be used in treatment to slow resistance evolution. However, collateral sensitivity interactions may depend on the local environmental conditions that bacteria experience, potentially reducing repeatability and clinical application. Here, we show that variation in local conditions (pH, temperature, and bile salts) can influence collateral sensitivity in two ways: by favoring different sets of mutants during bacterial resistance evolution (with different collateral sensitivities to other antibiotics) and by modifying expression of collateral effects for individual mutants. This suggests that translation from the lab to the clinic of new approaches exploiting collateral sensitivity will be influenced by local abiotic conditions. |
format | Online Article Text |
id | pubmed-8631318 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-86313182021-12-07 Collateral Sensitivity Interactions between Antibiotics Depend on Local Abiotic Conditions Allen, Richard C. Pfrunder-Cardozo, Katia R. Hall, Alex R. mSystems Research Article Mutations conferring resistance to one antibiotic can increase (cross-resistance) or decrease (collateral sensitivity) resistance to others. Antibiotic combinations displaying collateral sensitivity could be used in treatments that slow resistance evolution. However, lab-to-clinic translation requires understanding whether collateral effects are robust across different environmental conditions. Here, we isolated and characterized resistant mutants of Escherichia coli using five antibiotics, before measuring collateral effects on resistance to other paired antibiotics. During both isolation and phenotyping, we varied conditions in ways relevant in nature (pH, temperature, and bile). This revealed that local abiotic conditions modified expression of resistance against both the antibiotic used during isolation and other antibiotics. Consequently, local conditions influenced collateral sensitivity in two ways: by favoring different sets of mutants (with different collateral sensitivities) and by modifying expression of collateral effects for individual mutants. These results place collateral sensitivity in the context of environmental variation, with important implications for translation to real-world applications. IMPORTANCE When bacteria become resistant to an antibiotic, the genetic changes involved sometimes increase (cross-resistance) or decrease (collateral sensitivity) their resistance to other antibiotics. Antibiotic combinations showing repeatable collateral sensitivity could be used in treatment to slow resistance evolution. However, collateral sensitivity interactions may depend on the local environmental conditions that bacteria experience, potentially reducing repeatability and clinical application. Here, we show that variation in local conditions (pH, temperature, and bile salts) can influence collateral sensitivity in two ways: by favoring different sets of mutants during bacterial resistance evolution (with different collateral sensitivities to other antibiotics) and by modifying expression of collateral effects for individual mutants. This suggests that translation from the lab to the clinic of new approaches exploiting collateral sensitivity will be influenced by local abiotic conditions. American Society for Microbiology 2021-11-30 /pmc/articles/PMC8631318/ /pubmed/34846167 http://dx.doi.org/10.1128/mSystems.01055-21 Text en Copyright © 2021 Allen et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Allen, Richard C. Pfrunder-Cardozo, Katia R. Hall, Alex R. Collateral Sensitivity Interactions between Antibiotics Depend on Local Abiotic Conditions |
title | Collateral Sensitivity Interactions between Antibiotics Depend on Local Abiotic Conditions |
title_full | Collateral Sensitivity Interactions between Antibiotics Depend on Local Abiotic Conditions |
title_fullStr | Collateral Sensitivity Interactions between Antibiotics Depend on Local Abiotic Conditions |
title_full_unstemmed | Collateral Sensitivity Interactions between Antibiotics Depend on Local Abiotic Conditions |
title_short | Collateral Sensitivity Interactions between Antibiotics Depend on Local Abiotic Conditions |
title_sort | collateral sensitivity interactions between antibiotics depend on local abiotic conditions |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631318/ https://www.ncbi.nlm.nih.gov/pubmed/34846167 http://dx.doi.org/10.1128/mSystems.01055-21 |
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