Gene transfer from bacteria to mammalian cells.

Transfer of genetic information between phylogenetically remote bacterial genera [1], from bacteria to yeast [2] and from bacteria to plants [3] by plasmid conjugation has been described. However, direct DNA transfer from prokaryotes to mammalian cells has not yet been demonstrated. Certain bacterial species have evolved the ability to enter mammalian cells by inducing their own internalization [4]. We show that invasive strains of Shigella flexneri and Escherichia coli, that undergo lysis upon entry into mammalian cells because of impaired cell wall synthesis, can act as stable DNA delivery systems to their host. This direct gene transfer is efficient, of broad host cell range and the replicative or integrative vectors so delivered are stably inherited and expressed by the cell progeny. DNA delivery by abortive invasion of eukaryotic cells by bacteria is of potential interest for stimulation of mucosal immunity and for in vivo or ex vivo gene therapy of human diseases.