Differential effect of auxotrophies on the release of macromolecules by Salmonella enterica vaccine strains

Attenuated Salmonella enterica strains have been widely used as live carriers for vaccines and therapeutic molecules. Appropriate attenuation has been introduced into such bacteria for safety reasons and the improvement of strain properties. Here, we compared two strains that were rendered auxotroph for diaminopimelic acid or thymidine monophosphate precursors by deletion of the genes asd or thyA, respectively. Upon removal of the complementing compound from bacterial cultures, both strains quickly lose their property to form colonies. However, while the Δasd bacteria lysed almost immediately under such conditions, ΔthyA bacteria remained physically intact during the observation period. As a consequence, the Δasd bacteria released their intracellular content such as proteins or plasmids into the supernatant. In contrast, no intracellular component, either proteins or plasmids, could be recovered from the supernatants of ΔthyA bacteria upon depletion of thymidine. Thus, the release of macromolecules from the bacterial carrier occurs as a consequence of appropriate lethal attenuation. This might substitute for sophisticated secretion systems.