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Sweet Theranostics in Bitter Infections - Seek and Destroy

Ziel

Bacterial infections are now a global threat demanding novel treatments due to the appearance of resistances against antibiotics at a high pace. The ESKAPE pathogens are those with highest importance in the EU and chronic infections due to biofilm formation are a particular task. Noninvasive pathogen-specific imaging of the infected tissue is not clinically available. Its successful implementation will enable the choice of appropriate therapy and boost efficacy. Furthermore,
Gram-negative bacteria have a highly protective cellular envelope as an important resistance mechanism for drugs acting intracellularly, resulting in an alarmingly empty drug-pipeline.
To overcome this gap, I will establish Lectin-directed Theranostics targeting pathogens via their extracellular carbohydrate-binding proteins at the site of infection for specific imaging and treatment. This will be implemented for the highly resistant ESKAPE pathogen Pseudomonas aeruginosa through 3 different work packages.
WP1 Sweet Imaging: Design & conjugation of lectin-directed ligands to imaging probes, Optimization of ligand/linker, in vivo proof-of-concept imaging study.
WP2 Sweet Targeting: Delivery of antibiotics to the infection through covalent linking of lectindirecting groups. Employing different antibiotics, assessment of bactericidal potency and targeting efficiency. Manufacturing of nano-carriers with surface exposed lectin-directed ligands, noncovalent charging with antibiotics. In vitro and in vivo targeting.
WP3 Sweet SMART Targeting: Conjugates as SMART drugs: specific release of anti-biofilm lectin inhibitor and drug cargo upon contact with pathogen, development of linkers cleavable by pathogenic enzymes.
SWEETBULLETS will establish fundamentally novel lectin-directed theranostics to fight these deleterious infections and provide relief to nosocomially infected and cystic fibrosis patients. It is rapidly extendable towards other ESKAPE pathogens, e.g. Klebsiella spp..

Wissenschaftliches Gebiet

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Programm/Programme

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Aufforderung zur Vorschlagseinreichung

ERC-2016-STG

Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

ERC-STG - Starting Grant

Gastgebende Einrichtung

HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH
Netto-EU-Beitrag
€ 1 499 551,00
Adresse
INHOFFENSTRASSE 7
38124 Braunschweig
Deutschland

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Niedersachsen Braunschweig Braunschweig, Kreisfreie Stadt
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€ 1 499 551,00

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Letzte Aktualisierung: 13 Juni 2023

Mein Booklet

Permalink: https://cordis.europa.eu/project/id/716311/de

European Union, 2024