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LimitMDR SIGNED

Utilizing evolutionary interactions to limit multidrug resistance

Total Cost €

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EC-Contrib. €

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Partnership

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Project "LimitMDR" data sheet

The following table provides information about the project.

Coordinator
DANMARKS TEKNISKE UNIVERSITET 

Organization address
address: ANKER ENGELUNDSVEJ 1 BYGNING 101 A
city: KGS LYNGBY
postcode: 2800
website: www.dtu.dk

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

 Coordinator Country Denmark [DK]
 Total cost 1˙492˙453 €
 EC max contribution 1˙492˙453 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-05-01   to  2020-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    DANMARKS TEKNISKE UNIVERSITET DK (KGS LYNGBY) coordinator 1˙492˙453.00

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 Project objective

Drug resistance is limiting our ability to treat most infectious diseases and forms of cancer. Indeed this relentless evolution is the major driver of treatment failure for diseases that are responsible for over half of the global disease related mortality. Yet, the underlying principles that guide this evolutionary response are poorly understood, in particular with regards to understanding the impact of multidrug treatment. LimitMDR will characterize evolutionary trajectories leading to multidrug resistance in response to individual and combination drug treatment through the execution of large-scale adaptive evolution experiment with two bacterial pathogens followed by genome sequencing and phenotyping. This effort will enable testing of contrasting hypotheses regarding the evolution of multidrug resistance in response to combination treatment.

We will characterize the cause-and-effect of resistance and sensitivity mutations identified in our global data set and map comprehensive fitness landscapes of mutations accumulated during drug resistance evolution to understand the evolutionary dynamics underlying resistance evolution. To accomplish these bold goals we shall develop novel multiplexed methodologies enabling unprecedented scale of construction and phenotypic testing of identified mutations. While genetic epistasis is considered of key importance to resistance evolution most studies focus on mutations within an individual gene. Through the development of a novel experimental approach we shall elucidate complex epistatic interaction networks between mutations accumulated during resistance evolution.

Finally, we will conduct mechanistic studies to uncover the mechanisms of collateral sensitivity. These studies will shed light on this underappreciated phenomenon, which is of critical relevance to drug discovery and the evolution of drug resistance. In conclusion LimitMDR will develop groundbreaking novel methodologies and scientific insights that will c

 Publications

year authors and title journal last update
List of publications.
2019 Carola E. H. Rosenkilde, Christian Munck, Andreas Porse, Marius Linkevicius, Dan I. Andersson, Morten O. A. Sommer
Collateral sensitivity constrains resistance evolution of the CTX-M-15 β-lactamase
published pages: 618, ISSN: 2041-1723, DOI: 10.1038/s41467-019-08529-y
Nature Communications 10/1 2020-02-13
2017 Morten O. A. Sommer, Christian Munck, Rasmus Vendler Toft-Kehler, Dan I. Andersson
Prediction of antibiotic resistance: time for a new preclinical paradigm?
published pages: 689-696, ISSN: 1740-1526, DOI: 10.1038/nrmicro.2017.75
Nature Reviews Microbiology 15/11 2020-02-13
2018 Andreas Porse, Thea S. Schou, Christian Munck, Mostafa M. H. Ellabaan, Morten O. A. Sommer
Biochemical mechanisms determine the functional compatibility of heterologous genes
published pages: 522, ISSN: 2041-1723, DOI: 10.1038/s41467-018-02944-3
Nature Communications 9/1 2020-02-13
2017 Munck, Christian; Ellabaan, Mostafa; Klausen, Michael; Sommer, Morten
The resistome of common human pathogens
published pages: 26, ISSN: , DOI: 10.1101/140194
BioRxiv 1 2020-02-13
2018 Leonie Johanna Jahn, Andreas Porse, Christian Munck, Daniel Simon, Svetlana Volkova, Morten Otto Alexander Sommer
Chromosomal barcoding as a tool for multiplexed phenotypic characterization of laboratory evolved lineages
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-018-25201-5
Scientific Reports 8/1 2020-02-13
2018 Lejla Imamovic, Maria-Anna Misiakou, Eric van der Helm, Gianni Panagiotou, Maite Muniesa, Morten Otto Alexander Sommer
Complete Genome Sequence of Escherichia coli Strain WG5
published pages: e01403-17, ISSN: 2169-8287, DOI: 10.1128/genomeA.01403-17
Genome Announcements 6/2 2019-05-29
2017 Andreas Porse, Heidi Gumpert, Jessica Z. Kubicek-Sutherland, Nahid Karami, Ingegerd Adlerberth, Agnes E. Wold, Dan I. Andersson, Morten O. A. Sommer
Genome Dynamics of Escherichia coli during Antibiotic Treatment: Transfer, Loss, and Persistence of Genetic Elements In situ of the Infant Gut
published pages: , ISSN: 2235-2988, DOI: 10.3389/fcimb.2017.00126
Frontiers in Cellular and Infection Microbiology 7 2019-05-29
2018 Lejla Imamovic, Mostafa Mostafa Hashim Ellabaan, Ana Manuel Dantas Machado, Linda Citterio, Tune Wulff, Soren Molin, Helle Krogh Johansen, Morten Otto Alexander Sommer
Drug-Driven Phenotypic Convergence Supports Rational Treatment Strategies of Chronic Infections
published pages: 121-134.e14, ISSN: 0092-8674, DOI: 10.1016/j.cell.2017.12.012
Cell 172/1-2 2019-05-29
2017 Ida Lauritsen, Andreas Porse, Morten O. A. Sommer, Morten H. H. Nørholm
A versatile one-step CRISPR-Cas9 based approach to plasmid-curing
published pages: , ISSN: 1475-2859, DOI: 10.1186/s12934-017-0748-z
Microbial Cell Factories 16/1 2019-05-29
2017 Leonie J. Jahn, Christian Munck, Mostafa M. H. Ellabaan, Morten O. A. Sommer
Adaptive Laboratory Evolution of Antibiotic Resistance Using Different Selection Regimes Lead to Similar Phenotypes and Genotypes
published pages: , ISSN: 1664-302X, DOI: 10.3389/fmicb.2017.00816
Frontiers in Microbiology 8 2019-05-29
2017 Rachel A. Hickman, Christian Munck, Morten O. A. Sommer
Time-Resolved Tracking of Mutations Reveals Diverse Allele Dynamics during Escherichia coli Antimicrobial Adaptive Evolution to Single Drugs and Drug Pairs
published pages: , ISSN: 1664-302X, DOI: 10.3389/fmicb.2017.00893
Frontiers in Microbiology 8 2019-05-29
2016 Rebecca M. Lennen, Annika I. Nilsson Wallin, Margit Pedersen, Mads Bonde, Hao Luo, Markus J. Herrgård, Morten O. A. Sommer
Transient overexpression of DNA adenine methylase enables efficient and mobile genome engineering with reduced off-target effects
published pages: e36-e36, ISSN: 0305-1048, DOI: 10.1093/nar/gkv1090
Nucleic Acids Research 44/4 2019-05-29

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