Ricerc@Sapienza

Shigella is a highly adapted human pathogen, mainly found in the developing world and causing a severe enteric syndrome. Like in other life-threatening human pathogens, also in Shigella the regulation of virulence genes occurs at diverse levels and is modulated by environmental stimuli from the host. A central factor in this process is VirF, an activator belonging to the AraC family of transcriptional regulators whose expression is activated as soon as Shigella senses to have entered the host environment. Despite its crucial role as major player in the cascade of events leading to the activation of the virulent programme, its molecular characterization is insufficiently detailed and information on its mechanisms of action is still scarce.

The aim of this project is to investigate on new regulatory interactions involved in the optimization of the invasive programme of Shigella by deeper analyzing the structure and function of VirF. The project will be articulated into two research lines, which will coordinately exploit the specific competencies and know-how of the participating scientists and will be based on a multidisciplinary approach including bacterial genetics, molecular biology methodologies, and in vivo infection assays. In particular, we will analyze the capacity of VirF to form dimers or more complex aggregates and, following the recent identification by our group of a minor VirF form (VirF21), we will study its the role during the invasive process of Shigella.

AraC proteins are considered very interesting candidate targets in anti virulence strategies, due to their critical role in controlling virulence in pathogenic bacteria. Hence, a better understanding of the structure of the VirF proteins can be anticipated to positively impact on the development of new therapeutic approaches exploiting specific inhibitory compounds.