reproduction. Unlike the CRISPRs, which simply destroy infecting phages and thus totally block phage-mediated horizontal gene transfer (HGT), the SaPIs are major agents of phage–dependent HGT, as they only partially block phage reproduction and also package chromosomal fragments as well as their own genomes. Role in pathogenicity SaPIs were discovered on the basis of their carriage of the gene for toxic shock syndrome toxin-1 and they are uniquely responsible for staphylococcal toxic shock. They also carry other superantigen toxins as well as other virulence factors among which is a set of genes enabling their host strains to coagulate farm animal blood plasma. These genes encode different alleles of a coagulase, the von Willebrand factor-binding protein, which has a role in determining the animal host specificity of S. aureus. The toxin and other accessory genes are expressed by the integrated and repressed SaPI genomes, as are the toxin genes of converting prophages. Conversion to antibacterial agents One of the original SaPIs, SaPI2, has been converted to a non-antibiotic therapeutic agent for the treatment of staphylococcal and listerial infections. This conversion involved the removal of all toxin and other virulence genes, and of the capsid morphogenesis genes, and the addition, by cloning, of antibacterial genes including those encoding CRISPR/cas9 with spacers targeting conserved chromosomal genes. These cause a lethal double-stranded DNA cleavage in the target protospacer. Alternative cargos include CRISPR/dcas9 with spacers targeting and inhibiting genes that regulate bacterial virulence, or the gene for lysostaphin, a powerful staphylolytic enzyme. The production of these transformed SaPI2s, known as antibacterial drones (ABDs), is greatly enhanced by deleting the helper prophage’s terS gene so that only ABD DNA is packaged. The ABDs cure experimental staph infections in mice and are being further developed for clinical use. To preclude the development of resistance, ABDs for potential clinical use will always contain at least two different antibacterial modules that act by different mechanisms. References Mobile genetic elements