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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."

Field of science

  • /natural sciences/biological sciences/microbiology/bacteriology

Call for proposal

ERC-2011-ADG_20110310
See other projects for this call

Funding Scheme

ERC-AG - ERC Advanced Grant

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)

KOBENHAVNS UNIVERSITET
Denmark
EU contribution
€ 1 641 930,80
Address
Norregade 10
1165 Kobenhavn
Activity type
Higher or Secondary Education Establishments
Principal investigator
Kenn Gerdes (Prof.)
Administrative Contact
Tine Mathiesen (Mrs.)
UNIVERSITY OF NEWCASTLE UPON TYNE

Participation ended

United Kingdom
EU contribution
€ 813 179,20
Address
Kings Gate
NE1 7RU Newcastle Upon Tyne
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Amanda Gregory (Dr.)