Ricerc@Sapienza

The increase in available sequence data has uncovered genome complements that include from one to several chromosomes, some of which even endowed with a linear structure, and has paved the way for the debate on the elusive difference between chromosome and megaplasmid. While providing a number of clues on the evolution of bacteria and on the distribution of genes and operons, the knowledge derived from genomic sequencing still leaves open some fascinating questions: Why do some bacteria have a single chromosome, others more than one, and still others maintain relevant genes on mobile genetic elements? Why are virulence genes in some bacteria always confined on a plasmid?
Shigelal and enteroinvasive E.coli (EIEC) are intracellular pathogens causing bacillary dysentery, a severe enteric syndrome in humans. The pathogenicity of Shigella and EIEC depends on the presence of a large plasmid (pINV) carrying the genes required for the invasion of macrophages and epithelial cells.
Previously our research group have shown that that the pINV plasmid of EIEC is able to integrate into the host chromosome and that integration results in the silencing of all the pINV virulence genes. While these observations have led to the intriguing hypothesis that pINV integration might constitute a further strategy to ensure plasmid maintenance, relevant steps of the integration process and of the mechanisms responsible for the modification of the regulatory pathways are still undefined.
This project aims to understand whether the presence of virulence genes on a large plasmid in Shigella and EIEC is the result of an evolutionary pathway towards the optimization of gene expression, and to assess to what extent this peculiar genetic organization is required by the physiology of Shigella and EIEC strains.