Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Allen, Richard C., Pfrunder-Cardozo, Katia R., Hall, Alex R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2021
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
_version_ 1784607533945585664
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
work_keys_str_mv AT allenrichardc collateralsensitivityinteractionsbetweenantibioticsdependonlocalabioticconditions
AT pfrundercardozokatiar collateralsensitivityinteractionsbetweenantibioticsdependonlocalabioticconditions
AT hallalexr collateralsensitivityinteractionsbetweenantibioticsdependonlocalabioticconditions