Effect of tolerance on the evolution of antibiotic resistance under drug combinations

Jiafeng Liu, Orit Gefen, Irine Ronin, Maskit Bar-Meir*, Nathalie Q. Balaban

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

241 Scopus citations

Abstract

Drug combinations are widely used in clinical practice to prevent the evolution of resistance. However, little is known about the effect of tolerance, a different mode of survival, on the efficacy of drug combinations for preventing the evolution of resistance. In this work, we monitored Staphylococcus aureus strains evolving in patients under treatment. We detected the rapid emergence of tolerance mutations, followed by the emergence of resistance, despite the combination treatment. Evolution experiments on the clinical strains in vitro revealed a new way by which tolerance promotes the evolution of resistance under combination treatments. Further experiments under different antibiotic classes reveal the generality of the effect. We conclude that tolerance is an important factor to consider in designing combination treatments that prevent the evolution of resistance.

Original languageAmerican English
Pages (from-to)200-204
Number of pages5
JournalScience
Volume367
Issue number6474
DOIs
StatePublished - 10 Jan 2020

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© 2020 American Association for the Advancement of Science. All rights reserved.

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