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Sweet adhesins: Probing bacterial glycoproteins with novel tools to inspire future antibacterial strategies

Project description

Towards new strategies to fight infection

Adhesin proteins are crucial in bacterial infections. Their modification with highly unique sugars seems to be essential for their stability and adherence to host cells. In this context, the EU-funded STICKY SUGARS project will explore the potential of targeting bacterial adhesin sugars towards novel antibacterial strategies. Currently, there is a lack of suitable methods for the direct detection of sugars on adhesins. This has hindered the development of antibacterial strategies against them. As such, the project aims to revolutionise our understanding of adhesin sugars by designing an innovative approach that combines carbohydrate chemistry, enzymology, microbiology and molecular dynamics. By visualising and quantifying adhesin sugars directly on bacterial surfaces, it is possible to study their prevalence and response to antibacterial treatments, paving the way towards clinical applications.

Objective

With bacteria increasingly resistant to current antibiotics, new strategies to fight infection are needed. Bacterial adhesin proteins, which play an important role in the establishment of infection, appear to be promising targets for novel therapies. Adhesins enable the first contact between bacteria and host cells. We know that some adhesins are modified with highly unique sugars that are important for adhesin stability and adherence. However, we do not know how widespread this modification is, and whether it constitutes a good target for antibacterial strategies. A lack of suitable methods for the detection of bacterial adhesin sugars has impeded the detailed study of these sugars, blocking further efforts to develop antibacterial strategies against bacterial adhesin sugars. In this project, I aim to revolutionize our understanding of adhesin sugars, in terms of timing and prevalence of the modification, which is crucial information to start targeting adhesin sugars. To this end, I have designed an innovative approach that combines the strengths of carbohydrate chemistry, enzymology, microbiology and molecular dynamics to 1) establish straightforward methods to selectively visualize and quantify the adhesin sugars directly on the surface of bacterial cells; 2) detect the presence of adhesin sugars under changing growth conditions and in relevant clinical isolates; and 3) develop a computational method to predict the presence of sugars on adhesins that have not yet been identified. Recent findings from my team on the process of adhesin modification underscore the uniqueness of adhesin sugars, and this experience puts me in an ideal position to start this project. The overarching goal of STICKY SUGARS is to lay the foundation for the exploitation of adhesin sugars as antibacterial targets. By visualizing adhesin sugars directly on bacteria, we can observe their response to antibacterial treatments and pave the way toward clinical applications in the future.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2022-STG

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Host institution

RIJKSUNIVERSITEIT GRONINGEN
Net EU contribution
€ 1 499 251,00
Address
Broerstraat 5
9712CP Groningen
Netherlands
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 499 251,00

Beneficiaries (1)