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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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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. |
format | Online Article Text |
id | pubmed-8044428 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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