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Inhibitors of ECF transporters as novel antibacterial agents

Objective

Antimicrobial resistance is a global health threat, urgently calling for the development of novel anti-infective strategies. We will adopt a multidisciplinary approach to design, synthesize and optimize derivatives targeting ECF transporters as antibacterial agents. The ECF transporters are transmembrane proteins involved in the uptake of vitamins predominantly in Gram-positive pathogens (e.g. Streptococcus pneumoniae, Enterococcus faecalis, E. faecium, Staphylococcus aureus). Their inhibition prevents the uptake of vitamins from the environment, leading to starvation followed by cell death. Due to their critical role in the homeostasis of vitamins in bacteria as well as their absence in humans, ECF transporters are considered a promising novel antimicrobial target. We will thoroughly profile our inhibitors for their in vitro on-target and antibacterial activities. We will, on the one hand, further validate the cellular target through advanced target engagement studies and attempt to achieve a co-crystal structure using cryo-electron microscopy. Furthermore, evaluation of the inhibitors for their in vitro ADME-T properties and in vivo pharmacokinetic profiles will set the stage for in vivo infection models in mice. The extensive data that we will gather will enable us to nominate the most promising compound(s) for further multiparameter optimization en route to the nomination of a preclinical candidate. Ultimately, this opens access to novel anti-infectives with an unprecedented mode of action.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2023-POC

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Host institution

HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 150 000,00
Address
INHOFFENSTRASSE 7
38124 Braunschweig
Germany

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Region
Niedersachsen Braunschweig Braunschweig, Kreisfreie Stadt
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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Beneficiaries (1)

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