Titolo della tesi: Deciphering the mechanism of Shigella virulence regulation by intestinal factors: The key role of VirF protein
Shigella spp. are highly adapted human pathogens that cause bacillary dysentery. The complex infectious strategy of Shigella depends on the ability to invade, destroy, and cause inflammatory destruction of the intestinal epithelial barrier. The gene encoding the protein VirF, an AraC-like transcription factor (TF), is the master regulator of the virulence phenotype. VirF can activate downstream genetic determinants of virulence by inducing virB transcription in a cascade manner. Recent bioinformatics studies have provided further insight into the structure of the VirF protein. Like other members of AraC-XylS family proteins, VirF exhibits a "jelly roll" module, a hydrophobic pocket that can accommodate intestinal molecules such as saturated and unsaturated fatty acids, not excluding particular FAs known as diffusible signal factors (DSFs), involved in quorum-sensing signaling. These interactions regulate the activity of VirF and change its conformation so that VirF is no longer able to bind the virB promoter and the virulence cascade is interrupted. In addition, VirF also responds to several stimuli, including peptidoglycan receptor proteins (PGRPs). This interaction showed an increase in virF transcription and thus Shigella infectivity. A better understanding of VirF structure and its regulation could have a positive impact on the development of new therapeutic strategies. Inhibiting virulence instead of bacterial viability is a very effective approach to combat bacterial infections because it minimizes the emergence of antibiotic resistance.