Salmonella enterica serovar Typhimurium surA mutants are attenuated and effective live oral vaccines

A previously described attenuated TnphoA mutant (BRD441) of Salmonella ente rica serovar Typhimurium C5 (I. Miller, D. Maskell, C. Hormaeche, K. Johnso n, D. Pickard, and G. Dougan, Infect. Immun, 57:2758-2763, 1989) was charac terized, and the transposon was shown to be inserted in surA, a gene which encodes a peptidylprolyl-cis,trans-isomerase, A defined surA deletion mutat ion was introduced into S. enterica serovar Typhimurium C5 and the mutant s train, named S. enterica serovar Typhimurium BRD1115, was extensively chara cterized both in vitro and in vivo. S. enterica serovar Typhimurium BRD1115 was found to be defective in the ability to adhere to and invade eukaryoti c cells. Furthermore, S. enterica serovar Typhimurium BRD1115 was attenuate d by at least 3 log units when administered orally or intravenously to BALB /c mice. Complementation of the mutation with a plasmid carrying the intact surA gene almost completely restored the virulence of BRD1115. In addition , S. enterica serovar Typhimurium BRD1115 demonstrated potential as a vacci ne candidate, since mice immunized with BRD1115 were protected against subs equent challenge with S, enterica serovar Typhimurium C5, S. enterica serov ar Typhimurium BRD1115 also showed potential as a vehicle for the effective delivery of heterologous antigens, such as the nontoxic, protective fragme nt C domain of tetanus toxin, to the murine immune system.