In vivo adaptation of attenuated Salmonella typhimurium results in increased growth upon exposure to norepinephrine

Two studies were conducted to determine whether attenuated strains of Salmonella typhimurium, currently being investigated as possible vectors for mucosal vaccines, are able to respond to norepinephrine (NE). Bacteria were tested for NE responsiveness before and for 1 week after passage through juvenile rhesus monkeys. NE significantly increased the growth of the attenuated bacteria after being shed from the animal, but not before animal infection. Follow-up in vitro tests were performed by passaging the bacteria in Lauria-Bertani (LB) broth with or without selective antibiotic for the attenuation insert and supplementing with NE. NE increased the growth of bacteria passaged in LB broth with no selective antibiotic, but not in bacteria passaged in LB broth with selective antibiotic. These results show that the attenuated bacteria assumed to be safe for use as a vaccine are able to respond to environmental stimuli, such as NE, and change their characteristics. The results suggest that there may be problems with the stability of attenuated bacteria used as vectors for mucosal vaccines. (C) 1999 Elsevier Science Inc.