Hidden Suppressive Interactions Are Common in Higher-order Drug Combinations

Overview

Journal iScience

Publisher Cell Press

Date 2021 Apr 19

PMID 33870144

Citations 2

Authors

Natalie Ann Lozano-Huntelman

April Zhou

Elif Tekin

Mauricio Cruz-Loya

Bjorn Ostman

Sada Boyd

Van M Savage

Pamela Yeh

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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