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Disentangling the stringent response to engineer novel anti-persister drugs

Total Cost €


EC-Contrib. €






 DiStRes project word cloud

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

synthesis    engineering    group    persisters    facilitated    proof    slow    bacteria    broad    structurally    mutations    infections    antibiotics    stringent    clinical    structures    tools    cellular    highlight    rela    molecule    overarching    guarantees    modulators    validate    accuracy    hydrolysis    small    structural    catalogue    tolerate    antibiotic    spectrum    catalysed    breakthrough    rsh    strategy    settings    molecules    de    century    effectors    modern    compounds    candidates    inner    stress    ppgpp    single    despite    variety    tolerance    novo    cell    keystone    superbugs    midst    biotech    discover    fundamental    molecular    modulate    subpopulations    devised    chemical    biophysical    active    screen    turn    cells    ways    spot    pathogens    combines    microbiology    primary    eradicate    experiment    proteins    persistent    exercise    workings    genomic    refringent    biochemical    drugs    preliminary    mediated    antipersister    drug    last    modeling    dormant    resistant    customized    biology    resolution    revolution    conventional    designed    treatments    impinge    bacterial    source    mechanisms    enzymes    difficult   

Project "DiStRes" data sheet

The following table provides information about the project.


Organization address
postcode: 1050

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 Belgium [BE]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-COG
 Funding Scheme ERC-COG
 Starting year 2020
 Duration (year-month-day) from 2020-09-01   to  2025-08-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITE LIBRE DE BRUXELLES BE (BRUXELLES) coordinator 2˙000˙000.00


 Project objective

Bacterial “superbugs”, refringent to antibiotic treatments, have rapidly increased with the turn of the century. Slow growing, dormant cells (known as persisters) are subpopulations of bacteria that tolerate antibiotics and are considered a primary source of infections for antibiotic-resistant pathogens since they are difficult to eradicate in conventional ways. Mutations in RelA/SpoT (RSH), the effectors of the stringent response, promote antibiotic tolerance and persistent infections and are commonly selected in clinical settings of a variety of pathogens. However, despite the importance of the RSH-mediated stringent response, there is no comprehensive knowledge on the inner workings of the enzymes, or drugs that modulate the bacterial response to stress. Modern structurally biology is currently in the midst of a revolution comparable to that of the Genomic breakthrough of the end last century. This has facilitated access to structural information and increased the accuracy of the modeling and design of de novo structures of proteins and small molecules. Thus my overarching goal is to target key steps in the molecular mechanisms of ppGpp synthesis and hydrolysis catalysed by RSH enzymes, to discover active compounds against persisters. The highlight of this proposal is a new system biology approach that combines cellular microbiology (at a single cell resolution) with structural engineering, biophysical, biochemical and chemical-biology methods to design, screen and validate novel small molecule drug candidates targeting the stringent response. Based on preliminary keystone results from my group, we devised a proof of concept experiment for which we designed a catalogue of novel modulators of the stringent response customized to target bacteria in a specific or broad spectrum way. The success of this exercise guarantees this strategy will not only deliver new antipersister compounds and biotech tools, but will also impinge fundamental research in microbiology.

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The information about "DISTRES" are provided by the European Opendata Portal: CORDIS opendata.

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