Multidrug evolutionary strategies to reverse antibiotic resistance
Top Cited Papers
- 1 January 2016
- journal article
- review article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 351 (6268), aad3292
- https://doi.org/10.1126/science.aad3292
Abstract
Antibiotic treatment has two conflicting effects: the desired, immediate effect of inhibiting bacterial growth and the undesired, long-term effect of promoting the evolution of resistance. Although these contrasting outcomes seem inextricably linked, recent work has revealed several ways by which antibiotics can be combined to inhibit bacterial growth while, counterintuitively, selecting against resistant mutants. Decoupling treatment efficacy from the risk of resistance can be achieved by exploiting specific interactions between drugs, and the ways in which resistance mutations to a given drug can modulate these interactions or increase the sensitivity of the bacteria to other compounds. Although their practical application requires much further development and validation, and relies on advances in genomic diagnostics, these discoveries suggest novel paradigms that may restrict or even reverse the evolution of resistance.Keywords
Funding Information
- U.S. National Institutes of Health (R01-GM081617)
- European Research Council (281891)
- F. Hoffmann-La Roche Ltd
This publication has 127 references indexed in Scilit:
- Bacterial evolution of antibiotic hypersensitivityMolecular Systems Biology, 2013
- Evolutionary potential, cross‐stress behavior and the genetic basis of acquired stress resistance in Escherichia coliMolecular Systems Biology, 2013
- Collateral sensitivity as a strategy against cancer multidrug resistanceDrug Resistance Updates, 2012
- A Strategy for Antagonizing Quorum SensingMolecular Cell, 2011
- Phenotypic Landscape of a Bacterial CellCell, 2011
- Systematic exploration of synergistic drug pairsMolecular Systems Biology, 2011
- Bacterial charity work leads to population-wide resistanceNature, 2010
- Nonoptimal Microbial Response to Antibiotics Underlies Suppressive Drug InteractionsCell, 2009
- Discovery of a Small Molecule that Blocks Wall Teichoic Acid Biosynthesis in Staphylococcus aureusACS Chemical Biology, 2009
- Functional classification of drugs by properties of their pairwise interactionsNature Genetics, 2006