Evaluation of Typhimurium Lacking , , or as a Prophylactic Vaccine against Lethal Infection.

Non-typhoidal (NTS) is one of the primary causes of foodborne gastroenteritis; occasionally, it causes invasive infection in humans. Because of its broad host range, covering diverse livestock species, foods of animal origin pose a critical threat of NTS contamination. However, there is currently no licensed vaccine against NTS infection. FruR, also known as Cra (catabolite repressor/activator), was initially identified as the transcriptional repressor of the fructose () operon, and then found to activate or repress the transcription of many different genes associated with carbon and energy metabolism. In view of its role as a global regulator, we constructed a live attenuated vaccine candidate, Δ, and evaluated its prophylactic effect against NTS infection in mice. A Typhimurium mutant strain lacking was defective in survival inside macrophages and exhibited attenuated virulence in infected mice. Immunization with the Δ mutant stimulated the production of antibodies, including the IgG, IgM, and IgG subclasses, and afforded a protection of 100% to mice against the challenge of lethal infection with a virulent strain. The prophylactic effect obtained after Δ immunization was also validated by the absence of signs of hepatosplenomegaly, as these mice had comparable liver and spleen weights in comparison with healthy mice. These results suggest that the Δ mutant strain can be further exploited as a promising vaccine candidate against lethal infection.