Salmonella entericaSerovar TyphimuriumsurAMutants Are Attenuated and Effective Live Oral Vaccines

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Abstract
A previously described attenuated TnphoAmutant (BRD441) ofSalmonella entericaserovar Typhimurium C5 (I. Miller, D. Maskell, C. Hormaeche, K. Johnson, D. Pickard, and G. Dougan, Infect. Immun. 57:2758–2763, 1989) was characterized, and the transposon was shown to be inserted insurA, a gene which encodes a peptidylprolyl-cis,trans-isomerase. A definedsurAdeletion mutation was introduced intoS. entericaserovar Typhimurium C5 and the mutant strain, namedS. entericaserovar Typhimurium BRD1115, was extensively characterized both in vitro and in vivo.S. entericaserovar Typhimurium BRD1115 was found to be defective in the ability to adhere to and invade eukaryotic cells. Furthermore,S. entericaserovar Typhimurium BRD1115 was attenuated by at least 3 log units when administered orally or intravenously to BALB/c mice. Complementation of the mutation with a plasmid carrying the intactsurAgene almost completely restored the virulence of BRD1115. In addition,S. entericaserovar Typhimurium BRD1115 demonstrated potential as a vaccine candidate, since mice immunized with BRD1115 were protected against subsequent challenge withS. entericaserovar Typhimurium C5.S. entericaserovar Typhimurium BRD1115 also showed potential as a vehicle for the effective delivery of heterologous antigens, such as the nontoxic, protective fragment C domain of tetanus toxin, to the murine immune system.