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Infection and Immunity, March 2000, p. 1109-1115, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Salmonella enterica Serovar Typhimurium surA Mutants Are Attenuated and Effective Live Oral Vaccines

Mark Sydenham,1 Gillian Douce,1 Frances Bowe,2 Saddif Ahmed,2 Steve Chatfield,1,dagger and Gordon Dougan2,*

Medeva Vaccine Development Group, Department of Biochemistry,1 and Department of Biochemistry,2 Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom

Received 26 July 1999/Returned for modification 13 September 1999/Accepted 22 November 1999

A previously described attenuated TnphoA mutant (BRD441) of Salmonella enterica serovar 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 in surA, a gene which encodes a peptidylprolyl-cis,trans-isomerase. A defined surA deletion mutation was introduced into S. enterica serovar Typhimurium C5 and the mutant strain, named S. enterica serovar Typhimurium BRD1115, was extensively characterized both in vitro and in vivo. S. enterica serovar Typhimurium BRD1115 was found to be defective in the ability to adhere to and invade eukaryotic cells. Furthermore, S. enterica serovar 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 intact surA gene almost completely restored the virulence of BRD1115. In addition, S. enterica serovar Typhimurium BRD1115 demonstrated potential as a vaccine candidate, since mice immunized with BRD1115 were protected against subsequent challenge with S. enterica serovar Typhimurium C5. S. enterica serovar 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.

* Corresponding author. Mailing address: Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom. Phone: 44 171 594 5256. Fax: 44 171 594 5255. E-mail: g.dougan{at}ic.ac.uk.

dagger Present address: Microscience, Department of Infectious Diseases, Hammersmith Hospital, London W12 0NN.

Infection and Immunity, March 2000, p. 1109-1115, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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