suggesting that an ances­tral plasmid related to F was colonized successively by a number of mobile elements conferring different virulence functions. Similarly, the mosaic structure of the 46.4-kbp multidrug-resistance plasmid pSK41 from Staphylococcus aureus suggests that this plasmid has acquired its many resistance determinants by the insertion of both trans-posable elements and smaller plasmids into a conjugative progenitor plasmid (25). A large pathogenicity island bounded by insertion-sequence elements represents one-quarter of the 181.7-kbp virulence plasmid, pXO1, of B. anthracis and appears to have been acquired through transposition (32). This plasmid also harbors numerous other insertion sequences indicative of a highly recombinogenic history. These and many other recent examples indicate that large plasmids have evolved by accumulating additional genetic functions through successive, independent recombination events that are frequently mediated by transposable elements. The serial acquisition of viru­lence, antibiotic resistance and other determinants by plasmids allows the hosts that harbor them to invade and persist in increasingly hostile niches.