Obiettivo 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.. Campo scientifico natural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Parole chiave Lectin Carbohydrate Glycosciences Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-2016-STG - ERC Starting Grant Invito a presentare proposte ERC-2016-STG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-STG - Starting Grant Istituzione ospitante HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH Contribution nette de l'UE € 1 499 551,00 Indirizzo INHOFFENSTRASSE 7 38124 Braunschweig Germania Mostra sulla mappa Regione Niedersachsen Braunschweig Braunschweig, Kreisfreie Stadt Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 499 551,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH Germania Contribution nette de l'UE € 1 499 551,00 Indirizzo INHOFFENSTRASSE 7 38124 Braunschweig Mostra sulla mappa Regione Niedersachsen Braunschweig Braunschweig, Kreisfreie Stadt Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 499 551,00