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Structure and Thermodynamics of Adhesin-Mediated Virulence in Enterococci: Overcoming Fortified Biofilms

Project description

‘Untethering’ Gram-positive Enterococci bacteria to prevent virulence

Hospital-acquired infections caused by Gram-positive Enterococci bacteria pose a serious and growing clinical threat, driven by their ability to adhere to host cells, form protective biofilms and rapidly share antimicrobial resistance genes with neighbouring bacteria. Key to these processes are cell surface-anchored adhesion proteins (adhesins). One such adhesin is PrgB, which anchors bacteria to host tissues, stabilises cell-to-cell contact during resistance gene transfer and promotes biofilm development. With the support of the Marie Skłodowska-Curie Actions programme, the STAVE OFF project aims to identify the human PrgB receptors and resolve their binding interaction at atomic resolution, providing a molecular blueprint for developing new strategies to disarm these dangerous pathogens.

Objective

Gram-positive Enterococci account for a significant fraction of hospital-acquired infections but are often difficult to treat due to their proficiency in colonizing damaged host tissues, forming biofilms, and acquiring and spreading antimicrobial resistance (AMR). These AMR genes and additional virulence factors are often disseminated among the bacterial population via conjugation, the horizontal transfer of mobile genetic elements between cells in physical contact. Type 4 Secretion Systems (T4SSs) facilitate conjugation, and a key feature of many Gram-positive T4SSs are cell surface-anchored adhesion proteins. Adhesins not only stabilize mating pair junctions during conjugation but also promote biofilm formation and adherence to host cells during infection, making them a major factor in why hospital-acquired Gram-positive infections are so difficult to treat. One such adhesin is PrgB, which is encoded on the conjugative pCF10 plasmid from Enterococci faecalis. The Berntsson lab has previously characterized a subset of PrgB binding partners involved in biofilm formation, but the features of PrgB-host interactions required for infiltration and colonization remain unknown. In this proposed research, I aim to identify host-derived receptors that interact with PrgB, quantify the thermodynamic parameters of binding, and structurally resolve important binding interfaces. The resulting molecular details will explain how these adhesins confer virulence by promoting pathogenic colonization of host tissues, stabilizing mating pairs during conjugation, and initiating biofilm formation. This information will be important to the development of new strategies to mitigate the virulence of pathogenic Enterococci and Gram-positive bacteria more broadly.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

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

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

UMEA UNIVERSITET
Net EU contribution
€ 236 340,00
Address
UNIVERSITETOMRADET
901 87 UMEA
Sweden
Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
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Total cost
No data