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Bacterial Persistence

Bacterial Persistence

Objective

"Almost all bacterial species generate persisters, individual cells that are tolerant to antibiotics. Persisters have entered a dormant or slow growing state in which they are recalcitrant to the killing activity of most known antibiotics. The molecular mechanisms underlying bacterial persistence are unknown and there is a pressing need to develop new methods and approaches to study the phenomenon. We discovered recently that RNA endonucleases (RNases) encoded by toxin - antitoxin (TA) genes are required for persistence of the model bacterium Escherichia coli. We have shown that the RNases inhibit translation by cleavage of mRNA or tRNA and that their activation halts cell growth and induces persistence. We propose a testable model in which persistence is induced by stochastic activation of the RNases. Almost all free-living bacteria, including many serious pathogens, have TA genes, often in multiple or even many copies. For example, the major pathogen Mycobacterium tuberculosis, which can persist in the human body for many years, has at least 88 TA loci. This proposal describes a research program dedicated to develop novel general methods to study the persistence phenomenon and to test the hypothesis that TA loci are central to bacterial persistence. The implementation of novel, leading edge technologies will allow a profound understanding of the persistence phenomenon. Mechanistic insight into the persistence problem, in turn, will provide a basis for a rational approach to the development of drugs and drug administration regimes that may improve treatment of persistent infections."

Principal Investigator

Kenn Gerdes (Prof.)

Host institution

KOBENHAVNS UNIVERSITET

Address

Norregade 10
1165 Kobenhavn

Denmark

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 641 930,80

Principal Investigator

Kenn Gerdes (Prof.)

Administrative Contact

Tine Mathiesen (Mrs.)

Beneficiaries (2)

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KOBENHAVNS UNIVERSITET

Denmark

EU Contribution

€ 1 641 930,80

UNIVERSITY OF NEWCASTLE UPON TYNE

United Kingdom

EU Contribution

€ 813 179,20

Project information

Grant agreement ID: 294517

Status

Closed project

  • Start date

    1 May 2012

  • End date

    30 April 2017

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 2 455 110

  • EU contribution

    € 2 455 110

Hosted by:

KOBENHAVNS UNIVERSITET

Denmark