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 Salmo nella typhimurium, currently being investigated as possible vectors for muc osal vaccines, are able to respond to norepinephrine (NE). Bacteria were te sted for NE responsiveness before and for 1 week after passage through juve nile rhesus monkeys. NE significantly increased the growth of the attenuate d bacteria after being shed from the animal, but not before animal infectio n. Follow-up in vitro tests were performed by passaging the bacteria in Lau ria-Bertani (LB) broth with or without selective antibiotic for the attenua tion insert and supplementing with NE. NE increased the growth of bacteria passaged in LB broth with no selective antibiotic, but not in bacteria pass aged in LB broth with selective antibiotic. These results show that the att enuated bacteria assumed to be safe for use as a vaccine are able to respon d to environmental stimuli, such as NE, and change their characteristics. T he results suggest that there may be problems with the stability of attenua ted bacteria used as vectors for mucosal vaccines. (C) 1999 Elsevier Scienc e Inc.