title: Salmonella enterica serovar typhimurium surA mutants are attenuated and effective live oral vaccines.
abstract: 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.
authors.affiliation: Medeva Vaccine Development Group, Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Sydenham
authors.forename: G
authors.initials: G
authors.lastname: Douce
authors.forename: F
authors.initials: F
authors.lastname: Bowe
authors.forename: S
authors.initials: S
authors.lastname: Ahmed
authors.forename: S
authors.initials: S
authors.lastname: Chatfield
authors.forename: G
authors.initials: G
authors.lastname: Dougan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D002352:Carrier Proteins; D004251:DNA Transposable Elements; D005260:Female; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000502:physiology*; D012481:Salmonella Infections, Animal / Q000517:prevention & control; D012486:Salmonella typhimurium / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D002352:Carrier Proteins; D004251:DNA Transposable Elements; D015164:Vaccines, Inactivated; C098640:periplasmic peptidylprolyl cis-trans isomerase; D019696:Peptidylprolyl Isomerase