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RESUSCITATION

Bacterial persister regrowth

Total Cost €

0

EC-Contrib. €

0

Partnership

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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.

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

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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