Social networking: Understanding promiscuity in the transfer of bacterial virulence genes

The development of novel multiresistant hypervirulent strains from formerly avirulent or only weakly virulent strains is dramatically fuelled by the acquisition of mobile genetic elements carrying virulence factors. In spite of its relevance, the mechanisms underlying gene transfer among bacteria remain, in most cases, unidentified. In this project we will establish novel pathways by which bacteria exchange genetic information. Our results in support of this proposal suggest the existence of a hitherto unrecognized attribute of the Staphylococcal pathogenicity islands (SaPIs) that allows their promiscuous spread in nature. SaPIs are the prototypical members of a novel family of mobile genetic elements, the phage-inducible chromosomal islands (PICIs). They are important because they carry and disseminate clinically relevant virulence genes, including toxins and antibiotic resistance genes. We describe here the fascinating discovery that SaPIs have evolved to target conserved, essential phage mechanisms for their de-repression and widespread transfer in nature. This elegant strategy allows intra and inter-generic SaPI transfer, highlighting these elements as one of nature’s most fascinating subcellular parasites. In this project we will decipher the molecular basis of this unprecedented strategy. By achieving this objective we will establish new paradigms involving pathogenicity islands in bacterial evolution and virulence, and will provide strategies to block pathogenicity island dissemination and the emergence of novel bacterial virulent clones.