Tolerome SIGNED
Evolution of antibiotic tolerance in the 'wild': A quantitative approach
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0EC-Contrib. €
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Project "Tolerome" data sheet
The following table provides information about the project.
| Coordinator |
THE HEBREW UNIVERSITY OF JERUSALEM
Organization address contact info |
| Coordinator Country | Israel [IL] |
| Total cost | 1˙978˙750 € |
| EC max contribution | 1˙978˙750 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2015-CoG |
| Funding Scheme | ERC-COG |
| Starting year | 2016 |
| Duration (year-month-day) | from 2016-05-01 to 2021-04-30 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | THE HEBREW UNIVERSITY OF JERUSALEM | IL (JERUSALEM) | coordinator | 1˙978˙750.00 |
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Project objective
Bacterial ability to evolve strategies for evading antibiotic treatment is a fascinating example of an evolutionary process, as well as a major health threat. Despite efforts to understand treatment failure, we lack the means to prevent evolution of resistance when a new drug is released to the market. Most efforts are directed towards understanding the mechanisms of antibiotic resistance. Whereas ‘resistance’ is due to mutations that enable microorganisms to grow even at high concentrations of the drug, ‘tolerance’ is the ability to sustain a transient treatment, for example by entering a mode of transient dormancy. The importance of tolerance in the clinic has not been investigated as thoroughly as resistance. The presence of tolerant bacteria is not detected in the clinic because of the inherent difficulty of tracking dormant bacteria that often constitute only a minute fraction of the bacterial population. I hypothesize that bacterial dormancy may evolve quickly in the host under antibiotic treatment. This hypothesis is strengthened by our recent results demonstrating the rapid evolution of dormancy leading to tolerance in vitro, and by the increasing number of cases of treatment failure in the clinic not explained by resistance. My goal is to develop a multidisciplinary approach to detect, quantify and characterize tolerant bacteria in the clinic. Using my background in quantitative single-cell analyses, I will develop microfluidic devices for the rapid detection of tolerant bacteria in the clinic, systems biology tools to isolate and analyze dormant sub-populations directly from clinical isolates. I will search for the genetic mutations leading to tolerance, namely build what I term here the ‘tolerome’. The results will be analyzed in a mathematical framework of tolerance evolution. This approach should reveal the role of tolerance in the clinic and may lead to a paradigm shift in the way bacterial infections are characterized and treated.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2019 |
Nathalie Q. Balaban, Sophie Helaine, Kim Lewis, Martin Ackermann, Bree Aldridge, Dan I. Andersson, Mark P. Brynildsen, Dirk Bumann, Andrew Camilli, James J. Collins, Christoph Dehio, Sarah Fortune, Jean-Marc Ghigo, Wolf-Dietrich Hardt, Alexander Harms, Matthias Heinemann, Deborah T. Hung, Urs Jenal, Bruce R. Levin, Jan Michiels, Gisela Storz, Man-Wah Tan, Tanel Tenson, Laurence Van Melderen, Annel Definitions and guidelines for research on antibiotic persistence published pages: 441-448, ISSN: 1740-1526, DOI: 10.1038/s41579-019-0196-3 |
Nature Reviews Microbiology 17/7 | 2019-09-04 |
| 2018 |
Ariel Amir, Nathalie Q. Balaban Learning from Noise: How Observing Stochasticity May Aid Microbiology published pages: 376-385, ISSN: 0966-842X, DOI: 10.1016/j.tim.2018.02.003 |
Trends in Microbiology 26/4 | 2019-09-04 |
| 2018 |
Noga Mosheiff, Bruno M. C. Martins, Sivan Pearl-Mizrahi, Alexander Grünberger, Stefan Helfrich, Irina Mihalcescu, Dietrich Kohlheyer, James C. W. Locke, Leon Glass, Nathalie Q. Balaban Inheritance of Cell-Cycle Duration in the Presence of Periodic Forcing published pages: , ISSN: 2160-3308, DOI: 10.1103/physrevx.8.021035 |
Physical Review X 8/2 | 2019-09-04 |
| 2017 |
Asher Brauner, Noam Shoresh, Ofer Fridman, Nathalie Q. Balaban An Experimental Framework for Quantifying Bacterial Tolerance published pages: 2664-2671, ISSN: 0006-3495, DOI: 10.1016/j.bpj.2017.05.014 |
Biophysical Journal 112/12 | 2019-06-18 |
| 2017 |
Irit Levin-Reisman, Irine Ronin, Orit Gefen, Ilan Braniss, Noam Shoresh, Nathalie Q. Balaban Antibiotic tolerance facilitates the evolution of resistance published pages: 826-830, ISSN: 0036-8075, DOI: 10.1126/science.aaj2191 |
Science 355/6327 | 2019-06-18 |
| 2017 |
Irine Ronin, Naama Katsowich, Ilan Rosenshine, Nathalie Q Balaban A long-term epigenetic memory switch controls bacterial virulence bimodality published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.19599 |
eLife 6 | 2019-06-18 |
| 2017 |
Orit Gefen, Betty Chekol, Jacob Strahilevitz, Nathalie Q. Balaban TDtest: easy detection of bacterial tolerance and persistence in clinical isolates by a modified disk-diffusion assay published pages: 41284, ISSN: 2045-2322, DOI: 10.1038/srep41284 |
Scientific Reports 7 | 2019-06-18 |
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