A SALMONELLA-TYPHIMURIUM MUTANT UNABLE TO UTILIZE FATTY-ACIDS AND CITRATE IS AVIRULENT AND IMMUNOGENIC IN MICE

Salmonella typhimurium SR-11 is extremely virulent at a dose as low as 10(5) colony forming units (cfu) when administered perorally to BALB/ c mice. Utilizing mini-transposon mutagenesis, a mutant of S. typhimur ium SR-11 was isolated that was unable to utilize oleate and citrate a s carbon sources. This mutant, designated S. typhimurium SR-11 Fad(-) (Fatty acid), was found to utilize sugars under cya/crp control as sol e carbon sources, suggesting that the mutation is not in either of the se genes. In addition, SR-11 Fad- utilized pyruvate and succinate, but was unable to utilize either acetate or isocitrate as sole carbon sou rce. In contrast to SR-11, SR-11 Fad(-) was found to be avirulent, i.e . BALB/c mice were completely healthy after oral infection with 10(9) S. typhimurium SR-11 Fad(-) cells. Moreover, 21 days after SR-11 Fad(- ) infection, BALB/c mice were found to be protected against an oral ch allenge with 109 cells of S. typhimurium SR-11. (C) 1998 Federation of European Microbiological Societies. Published by Elsevier Science B.V . All rights reserved.