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cryo-EM structures of a Gram-positive type 4 secretion system

Project description

Mapping bacterial gene transfer to tackle antimicrobial resistance

Antimicrobial resistance (AMR) occurs when bacteria evolve to withstand antibiotics, making infections harder to treat and increasing the risk of severe illness or death. AMR spreads through genetic mutations and also via horizontal gene transfer, where bacteria exchange resistance genes often through structures called type 4 secretion systems (T4SS). With the support of the Marie Skłodowska-Curie Actions programme, the Cryo-GraPoTSS project aims to build the first high-resolution, in situ imaging of T4SS in Gram-positive bacteria. Using cryogenic electron microscopy and tomography, researchers will study Enterococcus faecalis, a Gram-positive bacterium responsible for many hospital-acquired infections. Project findings will help delineate the mechanism of AMR transfer and identify new targets to combat AMR.

Objective

Gram-positive (G+) bacteria, such as the Enterococcus species faecium and faecalis, cause around half of hospital-acquired infections. These infections are increasingly antimicrobial-resistant (AMR), which presents a major challenge for tackling the global burden of disease. AMR arises from mutant genes, which can be inherited, and also spread between bacterial species by conjugation through type 4 secretion systems (T4SS), which are protein complex. T4SS are an attractive target for new antibioitics, but development has proven difficult without detailed structural information on these molecular machines. Information is especially lacking for G+ species, which we will address.

This project will use cryogenic electron microscopy and tomography to study the T4SS of E. faecalis and obtain the first high-resolution and in situ structures of any G+ T4SS, combining my experience with the cryo-EM of membrane protein complexes and the host’s expertise in G+ T4SS. We will reveal the molecular architecture of a critical conjugation machine and its network of protein-protein interactions. This will enable the precise mechanism of gene transfer and essential (targetable) proteins to be determined.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

UMEA UNIVERSITET
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.

€ 236 340,00
Address
UNIVERSITETOMRADET
901 87 Umea
Sweden

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Region
Norra Sverige Övre Norrland Västerbottens län
Activity type
Higher or Secondary Education Establishments
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Total cost

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