ABSTRACT

To achieve gene transfer without killing the host cells, strains of S. flexneri have been developed which are attenuated by mutation, making them metabolically dependent on the host cell. Unlike the conjugation-type and fusion-type mechanisms, this new wave of cell-mediated gene transfer methods resulted from the invasion of animal cells by bacteria, followed by the lysis of the bacterial cells and the release of plasmid DNA. Although there are no available auxotrophic strains of L. monocytogenes that can invade host cells efficiently, wild-type strains can be used as delivery vectors. S. typhimurium has been used to express a number of different antigens, including Listeria monocytogenes virulence factors, the Chlamydia trachomatis major outer membrane protein and various tumor autoantigens. E. coli has also been transformed with the invasin gene from Yersinia pseudotuberculosis, which allowed the bacteria to invade the host cell but not escape from the phagocytic vesicle, thus mimicking the infection strategy of Salmonella vectors.