Journal
VACCINES
Volume 10, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/vaccines10091413
Keywords
Salmonella vaccine; Salmonella infection; fruR; cra
Categories
Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [2017R1A2B4003834]
- National Research Foundation of Korea [2017R1A2B4003834] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Non-typhoidal Salmonella (NTS) is a major cause of foodborne gastroenteritis and can cause invasive infection in humans. A live attenuated vaccine candidate, Delta fruR, was constructed and shown to provide 100% protection against NTS infection in mice. The Delta fruR mutant stimulated antibody production and reduced virulence in infected mice.
Non-typhoidal Salmonella (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 (fru) 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, Delta fruR, and evaluated its prophylactic effect against NTS infection in mice. A Salmonella Typhimurium mutant strain lacking fruR was defective in survival inside macrophages and exhibited attenuated virulence in infected mice. Immunization with the Delta fruR 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 Salmonella strain. The prophylactic effect obtained after Delta fruR 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 Delta fruR mutant strain can be further exploited as a promising vaccine candidate against Salmonella lethal infection.
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