Distinguishing between resistance, tolerance and persistence to antibiotic treatment

Abstract

Antibiotic tolerance is associated with the failure of antibiotic treatment and the relapse of many bacterial infections. However, unlike resistance, which is commonly measured using the minimum inhibitory concentration (MIC) metric, tolerance is poorly characterized, owing to the lack of a similar quantitative indicator. This may lead to the misclassification of tolerant strains as resistant, or vice versa, and result in ineffective treatments. In this Opinion article, we describe recent studies of tolerance, resistance and persistence, outlining how a clear and distinct definition for each phenotype can be developed from these findings. We propose a framework for classifying the drug response of bacterial strains according to these definitions that is based on the measurement of the MIC together with a recently defined quantitative indicator of tolerance, the minimum duration for killing (MDK). Finally, we discuss genes that are associated with increased tolerance — the 'tolerome' — as targets for treating tolerant bacterial strains.

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Figure 1: Characteristic drug responses of resistance, tolerance and persistence.
Figure 2: Tolerance arises from slow growth or lag phase.

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Acknowledgements

The authors thank N. Shoresh for illuminating discussions regarding this manuscript, and the members of the Balaban laboratory, I. Kaspy and G. Glaser for comments and suggestions. This work is supported by the Minerva Center for Stochastic Decision Making in Microorganisms, a European Research Council (ERC) Starting Grant (260871) and the Israel Science Foundation (492/15).

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Correspondence to Nathalie Q. Balaban.

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Brauner, A., Fridman, O., Gefen, O. et al. Distinguishing between resistance, tolerance and persistence to antibiotic treatment. Nat Rev Microbiol 14, 320–330 (2016). https://doi.org/10.1038/nrmicro.2016.34

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