Design principles of collateral sensitivity-based dosing strategies

Collateral sensitivity (CS)-based antibiotic treatments, where increased resistance to one antibiotic leads to increased sensitivity to a second antibiotic, may have the potential to limit the emergence of antimicrobial resistance. However, it remains unclear how to best design CS-based treatment sc...

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Autores principales: Aulin, Linda B. S., Liakopoulos, Apostolos, van der Graaf, Piet H., Rozen, Daniel E., van Hasselt, J. G. Coen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479078/
https://www.ncbi.nlm.nih.gov/pubmed/34584086
http://dx.doi.org/10.1038/s41467-021-25927-3
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author Aulin, Linda B. S.
Liakopoulos, Apostolos
van der Graaf, Piet H.
Rozen, Daniel E.
van Hasselt, J. G. Coen
author_facet Aulin, Linda B. S.
Liakopoulos, Apostolos
van der Graaf, Piet H.
Rozen, Daniel E.
van Hasselt, J. G. Coen
author_sort Aulin, Linda B. S.
collection PubMed
description Collateral sensitivity (CS)-based antibiotic treatments, where increased resistance to one antibiotic leads to increased sensitivity to a second antibiotic, may have the potential to limit the emergence of antimicrobial resistance. However, it remains unclear how to best design CS-based treatment schedules. To address this problem, we use mathematical modelling to study the effects of pathogen- and drug-specific characteristics for different treatment designs on bacterial population dynamics and resistance evolution. We confirm that simultaneous and one-day cycling treatments could supress resistance in the presence of CS. We show that the efficacy of CS-based cycling therapies depends critically on the order of drug administration. Finally, we find that reciprocal CS is not essential to suppress resistance, a result that significantly broadens treatment options given the ubiquity of one-way CS in pathogens. Overall, our analyses identify key design principles of CS-based treatment strategies and provide guidance to develop treatment schedules to suppress resistance.
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spelling pubmed-84790782021-10-22 Design principles of collateral sensitivity-based dosing strategies Aulin, Linda B. S. Liakopoulos, Apostolos van der Graaf, Piet H. Rozen, Daniel E. van Hasselt, J. G. Coen Nat Commun Article Collateral sensitivity (CS)-based antibiotic treatments, where increased resistance to one antibiotic leads to increased sensitivity to a second antibiotic, may have the potential to limit the emergence of antimicrobial resistance. However, it remains unclear how to best design CS-based treatment schedules. To address this problem, we use mathematical modelling to study the effects of pathogen- and drug-specific characteristics for different treatment designs on bacterial population dynamics and resistance evolution. We confirm that simultaneous and one-day cycling treatments could supress resistance in the presence of CS. We show that the efficacy of CS-based cycling therapies depends critically on the order of drug administration. Finally, we find that reciprocal CS is not essential to suppress resistance, a result that significantly broadens treatment options given the ubiquity of one-way CS in pathogens. Overall, our analyses identify key design principles of CS-based treatment strategies and provide guidance to develop treatment schedules to suppress resistance. Nature Publishing Group UK 2021-09-28 /pmc/articles/PMC8479078/ /pubmed/34584086 http://dx.doi.org/10.1038/s41467-021-25927-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Aulin, Linda B. S.
Liakopoulos, Apostolos
van der Graaf, Piet H.
Rozen, Daniel E.
van Hasselt, J. G. Coen
Design principles of collateral sensitivity-based dosing strategies
title Design principles of collateral sensitivity-based dosing strategies
title_full Design principles of collateral sensitivity-based dosing strategies
title_fullStr Design principles of collateral sensitivity-based dosing strategies
title_full_unstemmed Design principles of collateral sensitivity-based dosing strategies
title_short Design principles of collateral sensitivity-based dosing strategies
title_sort design principles of collateral sensitivity-based dosing strategies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479078/
https://www.ncbi.nlm.nih.gov/pubmed/34584086
http://dx.doi.org/10.1038/s41467-021-25927-3
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