Biochemical analysis of bacterial proteins involved in pathogenesis to identify alternative strategies to antibiotics and/or to enhance their effects

Biochemical analysis of bacterial proteins involved in pathogenesis to identify alternative strategies to antibiotics and/or to enhance their effects

Research Group: Giampiero Pietrocola, Angelica Pellegrini

Antimicrobial resistance (AMR) undermines the efficacy of life-saving antimicrobial treatments and has emerged as a global health crisis in the contemporary medical landscape, deeply threatening our ability to treat infectious diseases. For these reasons, research and investment in the development of new antimicrobial strategies has become imperative. Pathogenic bacteria produce a range of virulence factors that enable them to colonise host tissues and evade the immune system’s defences. However, the effects of these factors on the host are still largely unknown. Only a thorough understanding of their characteristics can unravel the mechanisms by which bacteria infect humans, paving the way for alternative strategies to the use of antibiotics and/or to enhance their effects. In this context, our laboratory is dedicated to the biochemical characterisation of protein virulence factors expressed by major human pathogenic bacteria that have developed marked resistance to antibiotics. The PhD student will have the opportunity to clone specific virulence factors using molecular biology techniques and purify them by chromatography, then apply advanced biochemical techniques to understand the molecular mechanisms that regulate the interaction with the host. The PhD student will also have the opportunity to test families of synthetic small molecules using in vitro assays and in vivo infection models to assess their inhibitory potential on the virulence factors under investigation.

Recent Publications:

  • Pellegrini A, Motta C, Bellan Menegussi E, Pierangelini A, Viglio S, Coppolino F, Beninati C, De Filippis V, Barbieri G, Pietrocola G. The serine-rich repeat glycoprotein Srr2 mediates Streptococcus agalactiae interaction with host fibronectin. BMC Microbiol. 2024;24(1):221. doi: 10.1186/s12866-024-03374-6.
  • Motta C, Pellegrini A, Camaione S, Geoghegan J, Speziale P, Barbieri G, Pietrocola G. von Willebrand factor-binding protein (vWbp)-activated factor XIII and transglutaminase 2 (TG2) promote cross-linking between FnBPA from Staphylococcus aureus and fibrinogen. Sci Rep. 2023;13(1):11683. doi: 10.1038/s41598-023-38972-3.
  • Alfeo MJ, Pagotto A, Barbieri G, Foster TJ, Vanhoorelbeke K, De Filippis V, Speziale P, Pietrocola G. Staphylococcus aureus iron-regulated surface determinant B (IsdB) protein interacts with von Willebrand factor and promotes adherence to endothelial cells. Sci Rep. 2021;11(1):22799. doi: 10.1038/s41598-021-02065-w.