title: 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.
authors.affiliation: Racah Institute of Physics and the Harvey M. Kruger Family Center for Nanoscience and Nanotechnology, Edmond J. Safra Campus, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Asher
authors.initials: A
authors.lastname: Brauner
authors.affiliation: Racah Institute of Physics and the Harvey M. Kruger Family Center for Nanoscience and Nanotechnology, Edmond J. Safra Campus, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Fridman
authors.affiliation: Racah Institute of Physics and the Harvey M. Kruger Family Center for Nanoscience and Nanotechnology, Edmond J. Safra Campus, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Gefen
authors.affiliation: Racah Institute of Physics and the Harvey M. Kruger Family Center for Nanoscience and Nanotechnology, Edmond J. Safra Campus, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Nathalie Q
authors.initials: NQ
authors.lastname: Balaban
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004361:Drug Tolerance; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents