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

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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