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Tolerome SIGNED

Evolution of antibiotic tolerance in the 'wild': A quantitative approach

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EC-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
address: EDMOND J SAFRA CAMPUS GIVAT RAM
city: JERUSALEM
postcode: 91904
website: www.huji.ac.il

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
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 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.

# participants  country  role  EC contrib. [€] 
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
List of publications.
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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