Molecular biology of the PICIs, a novel and widespread family of mobile genetic elements involved in bacterial virulence

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The idea that bacterial genomes within one single species can vary widely in gene content is not new. However, it was only with the advent of the genomic era that the phenomenon has been properly perceived. Not only was the genome size different; a significant number of the genes present in different strains from a specific species were not even related i.e. had no homologous genes in the others. Most of these genes were carried on mobile genetics elements (MGEs), including plasmids, bacteriophages, pathogenicity islands, transposons or integrons, which can be potentially transferred among bacteria. Thus, it is now assumed that horizontal gene transfer (HGT) has had an extremely important role in bacterial evolution. Indeed it has been estimated that some 20% of the extant genetic content of any given bacterial species has been acquired from other organisms. Perhaps half of this 20% consists of MGEs, which have moved freely within and between species and have occasionally crossed intergeneric boundaries. With facultative pathogens, MGEs are largely responsible for antibiotic resistance, environmental adaptations and the wide variety of adaptations to life in host tissues that we perceive as pathogenesis. In most pathogenic bacteria, all known classes of bacterial MGEs may contribute to pathogenesis, and it is particularly striking that essentially all of the bacterial toxins that cause specific toxin-mediated diseases - toxinoses - such as PVL pneumonia, diphtheria, dysentery, toxic shock syndrome, food poisoning, necrotizing pneumonia, scalded skin syndrome, botulism, hemolytic-uremic syndrome or necrotizing fasciitis, are encoded by MGEs.This application represents the culmination of a long and highly productive research program starting in 2003 and extending to the present. During this time we have characterised a novel family of mobile staphylococcal pathogenicity islands, the SaPIs, which are the only source of several important superantigens, including toxic shock syndrome toxin-1 and enterotoxins B and C, as well as the source for other virulence factors related with host adaptation. Now, we hypothesise that similar elements occur widely in bacteria, conforming a unique class of mobile genetic elements, the phage-inducible chromosomal islands (PICIs). We suggest that the PICIs have spread widely throughout the bacterial world, and have diverged much more slowly than their host organisms. If true, these findings represent the discovery of a new class of MGE, which have a broad impact on lateral gene transfer and virulence in the bacterial world.The overall goal of this project is double: on one hand, we will try to confirm the existence of this novel and widespread family of mobile genetic elements, the PICIs. On the other hand, we will try to demonstrate that these elements have an important role in virulence by encoding novel and uncharacterised virulent genes. We propose that the successful completion of our research will introduce a new paradigm in the understanding of the biology of pathogenicity islands and therefore of bacterial evolution. Our studies will greatly enhance understanding of the evolution of pathogenic bacteria and apparition of novel virulence clones through the acquisition of MGEs, especially across genera.