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An innovative peptide system for novel drugs targeting microbial Repeats-In-Toxin adhesins

Project description

Novel peptides targeting microbial repeats-in-toxin adhesins

Even infectious diseases with long history such as cholera still present a healthcare challenge and significant social cost. Cholera is an acute diarrhoeal disease that can kill within hours if left untreated, with several millions of estimated cases annually and over 100 000 deaths worldwide. Gram-negative bacteria produce repeats-in-toxin adhesion proteins (RTX adhesins) to facilitate their adhesion. A recent study demonstrated that the RTX adhesin (FrhA) of cholera bacteria facilitates attaching to and infection of human intestinal cells. Researchers also discovered compounds that bind to FrhA, suggesting these could help prevent cholera infection. The EU-funded PEPTOX project is based on the hypothesis that binding of FrhA can also detach already-adhered bacteria. Work aims to optimise the synthesis and characterisation of the novel compounds and demonstrate blockage of cholera adhesion in an in vitro cellular model.

Objective

Despite progress in infection treatment in the last decades, the prevalence and mortality of infections still poses a heavy burden over humankind. The development of antimicrobial resistance and the rapid mutagenesis of bacteria that leads to inefficiency of vaccines, play an important role in maintaining infections high level of threat. Even diseases that have plagued us for centuries, such as cholera, still challenge medical professionals and cause a significant social cost. New therapeutic approaches that promise a higher success rate are a pressing need. We recently discovered a high similarity between an ice-binding protein and the RTX adhesin (FrhA) used by the bacteria of cholera to attach to and infect the human intestine. Moreover, we discovered compounds that bind to FrhA and successfully block it, suggesting these could help prevent cholera’s infection. If these can also detach already adhered bacteria, cholera could be effectively removed and cured. In this ERC PoC PEPTOX project, we aim to optimise the synthesis and characterization of the newly discovered compounds and demonstrate blockage of cholera adhesion in an in vitro cellular model.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

ERC-POC - Proof of Concept Grant

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Call for proposal

(opens in new window) ERC-2019-PoC

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Host institution

TECHNISCHE UNIVERSITEIT EINDHOVEN
Net EU contribution
€ 150 000,00
Address
GROENE LOPER 3
5612 AE Eindhoven
Netherlands
Region
Zuid-Nederland Noord-Brabant Zuidoost-Noord-Brabant
Activity type
Higher or Secondary Education Establishments
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Total cost
No data

Beneficiaries (1)