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Hidden suppressive interactions are common in higher-order drug combinations

The rapid increase of multi-drug resistant bacteria has led to a greater emphasis on multi-drug combination treatments. However, some combinations can be suppressive—that is, bacteria grow faster in some drug combinations than when treated with a single drug. Typically, when studying interactions, t...

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Autores principales: Lozano-Huntelman, Natalie Ann, Zhou, April, Tekin, Elif, Cruz-Loya, Mauricio, Østman, Bjørn, Boyd, Sada, Savage, Van M., Yeh, Pamela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044428/
https://www.ncbi.nlm.nih.gov/pubmed/33870144
http://dx.doi.org/10.1016/j.isci.2021.102355
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author Lozano-Huntelman, Natalie Ann
Zhou, April
Tekin, Elif
Cruz-Loya, Mauricio
Østman, Bjørn
Boyd, Sada
Savage, Van M.
Yeh, Pamela
author_facet Lozano-Huntelman, Natalie Ann
Zhou, April
Tekin, Elif
Cruz-Loya, Mauricio
Østman, Bjørn
Boyd, Sada
Savage, Van M.
Yeh, Pamela
author_sort Lozano-Huntelman, Natalie Ann
collection PubMed
description The rapid increase of multi-drug resistant bacteria has led to a greater emphasis on multi-drug combination treatments. However, some combinations can be suppressive—that is, bacteria grow faster in some drug combinations than when treated with a single drug. Typically, when studying interactions, the overall effect of the combination is only compared with the single-drug effects. However, doing so could miss “hidden” cases of suppression, which occur when the highest order is suppressive compared with a lower-order combination but not to a single drug. We examined an extensive dataset of 5-drug combinations and all lower-order—single, 2-, 3-, and 4-drug—combinations. We found that a majority of all combinations—54%—contain hidden suppression. Examining hidden interactions is critical to understanding the architecture of higher-order interactions and can substantially affect our understanding and predictions of the evolution of antibiotic resistance under multi-drug treatments.
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spelling pubmed-80444282021-04-16 Hidden suppressive interactions are common in higher-order drug combinations Lozano-Huntelman, Natalie Ann Zhou, April Tekin, Elif Cruz-Loya, Mauricio Østman, Bjørn Boyd, Sada Savage, Van M. Yeh, Pamela iScience Article The rapid increase of multi-drug resistant bacteria has led to a greater emphasis on multi-drug combination treatments. However, some combinations can be suppressive—that is, bacteria grow faster in some drug combinations than when treated with a single drug. Typically, when studying interactions, the overall effect of the combination is only compared with the single-drug effects. However, doing so could miss “hidden” cases of suppression, which occur when the highest order is suppressive compared with a lower-order combination but not to a single drug. We examined an extensive dataset of 5-drug combinations and all lower-order—single, 2-, 3-, and 4-drug—combinations. We found that a majority of all combinations—54%—contain hidden suppression. Examining hidden interactions is critical to understanding the architecture of higher-order interactions and can substantially affect our understanding and predictions of the evolution of antibiotic resistance under multi-drug treatments. Elsevier 2021-03-26 /pmc/articles/PMC8044428/ /pubmed/33870144 http://dx.doi.org/10.1016/j.isci.2021.102355 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Lozano-Huntelman, Natalie Ann
Zhou, April
Tekin, Elif
Cruz-Loya, Mauricio
Østman, Bjørn
Boyd, Sada
Savage, Van M.
Yeh, Pamela
Hidden suppressive interactions are common in higher-order drug combinations
title Hidden suppressive interactions are common in higher-order drug combinations
title_full Hidden suppressive interactions are common in higher-order drug combinations
title_fullStr Hidden suppressive interactions are common in higher-order drug combinations
title_full_unstemmed Hidden suppressive interactions are common in higher-order drug combinations
title_short Hidden suppressive interactions are common in higher-order drug combinations
title_sort hidden suppressive interactions are common in higher-order drug combinations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044428/
https://www.ncbi.nlm.nih.gov/pubmed/33870144
http://dx.doi.org/10.1016/j.isci.2021.102355
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