[STAVE OFF] Structure and Thermodynamics of Adhesin-Mediated Virulence in Enterococci: Overcoming Fortified Biofilms
Ente: EC
Scadenza: 2029-05-31
Importo max: 236.340 EUR
Paese: EU
Descrizione
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.
Settori: Horizon Europe Topics
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