Ricerc@Sapienza

Shigella is a facultative intracellular pathogen causing human bacillary dysentery, also known as shigellosis, an acute infection of the large intestine. The primary regulator of the virulence phenotype is VirF, a DNA-binding protein belonging to the AraC family of transcriptional regulators. The virF gene, located on a large virulence plasmid (pINV), is expressed only within the host, mainly in response to the temperature transition occurring when the bacterium transits from the outer environment to the intestinal milieu. Like other members of the AraC family, VirF has a conserved, carboxy-terminal DNA-binding domain with two helix-turn-helix (HTH) motifs, while the N - terminal domain of VirF promotes dimerization. Recent bioinformatics analyses have shown that VirF protein has a ¿Jelly roll¿ motif, a protein fold containing a binding pocket enclosed. This suggests a mechanism by which still unidentified molecules can interact with VirF and thus influence its activity. Previously published results about a similar protein suggest that the compounds involved in this interaction could be intestinal metabolites that contribute to the programmed expression of the virulence system within the host. The characterization and identification of these molecules may pave the way for the development of antivirulence compounds as therapeutic agents in the treatment of shigellosis.