Use of lambda phage S and R gene products in an inducible lysis system forVibrio cholerae- and Salmonella enterica serovar typhimurium-based DNA vaccine delivery systems

Novel methods for adapting DNA vaccine technology to the prevention of muco sal diseases are greatly needed. Here me show that regulated expression of phage lambda lysis genes S and R causes dramatic lysis of both Vibrio chole rae and Salmonella enterica serovar Typhimurium cells with concomitant rele ase of plasmid DNA into the surrounding media. We also used single and doub le DNase mutant strains to show that secreted V. cholerae DNases can advers ely affect the integrity of DNA molecules released upon lysis. These result s suggest that incorporation of lambda SR-mediated lysis constructs and DNA stabilizing mutations into candidate live attenuated bacterial vaccines of fers a promising approach for the development of effective mucosal DNA deli very vectors for humans.