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RESUSCITATION

Bacterial persister regrowth

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 RESUSCITATION project word cloud

Explore the words cloud of the RESUSCITATION project. It provides you a very rough idea of what is the project "RESUSCITATION" about.

detoxifying    discovery    activates    engulfment    despite    14    generate    plan    inducing    entry    persistence    ultimately    unravel    regrowth    pending    re    action    antitoxin    removed    force    offspring    environment    toxin    defence    systematic    bacteria    antibiotic    encounter    couple    resuscitation    consolidation    diseases    pth    begin    progress    form    relapses    mechanisms    intoxication    tolerant    enzyme    salmonella    underlying    counteracting    transiently    enzymes    biology    modules    characterization    proven    resumption    antibiotics    extend    implication    arrest    persister    toxins    interaction    exit    tact    first    forming    repertoire    persist    sensitized    question    persisters    intend    group    host    vs    multidrug    pressure    dissect    balance    proportions    additionally    identification    infectious    resuming    ways    unknown    lag    powerful    respectively    experimental    macrophages    cells    detoxification    model   

Project "RESUSCITATION" data sheet

The following table provides information about the project.

Coordinator
IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE 

Organization address
address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
city: LONDON
postcode: SW7 2AZ
website: http://www.imperial.ac.uk/

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 United Kingdom [UK]
 Total cost 1˙499˙996 €
 EC max contribution 1˙499˙996 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-STG
 Funding Scheme ERC-STG
 Starting year 2018
 Duration (year-month-day) from 2018-02-01   to  2023-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE UK (LONDON) coordinator 1˙499˙996.00

Map

 Project objective

This proposal aims to provide insight into persister resuscitation. Persisters are multidrug-tolerant cells that are transiently non-growing and able to generate viable offspring by resuming growth when antibiotic pressure is removed. Despite their implication in relapses of many infectious diseases, and progress in understanding how persisters form through the action of toxin-antitoxin modules, the mechanisms underlying resuscitation of these persisters are still unknown. The interaction between Salmonella and host macrophages has proven to be a powerful and relevant model to study persister biology since the bacteria specifically respond to engulfment by the host defence cells by forming high proportions of persisters. Upon encounter with the host, Salmonella activates 14 toxins to arrest growth and persist in this environment. With the recent discovery of a detoxifying enzyme (Pth) counteracting the action of a persister-inducing toxin (TacT), thus allowing growth resumption of Salmonella persisters, we can now begin to address the pending question of persister regrowth. The consolidation of my research group around the experimental plan proposed here, will enable us to dissect the balance between intoxication vs. detoxification or entry vs. exit from persistence induced by Tact and Pth respectively. This is the first couple of toxin/detoxifying enzymes to be identified. I intend to extend this knowledge to the whole repertoire of toxins involved in Salmonella persister formation through systematic identification and characterization of the detoxifying mechanisms allowing resuscitation. Additionally I will investigate the lag phase leading to regrowth of persisters; and target the toxins involved in persister formation to force persisters out of growth arrest. This work will unravel persister resuscitation and could ultimately provide ways to force persisters out of that state so they become re-sensitized to antibiotics.

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