title: Salmonella enterica serovar Typhimurium mutants completely lacking the F(0)F(1) ATPase are novel live attenuated vaccine strains.
abstract: The F(0)F(1) ATPase plays a central role in both the generation of ATP and the utilisation of ATP for cellular processes such as rotation of bacterial flagella. We have deleted the entire operon encoding the F(0)F(1) ATPase, as well as genes encoding individual F(0) or F(1) subunits, in Salmonella enteric serovar Typhimurium. These mutants were attenuated for virulence, as assessed by bacterial counts in the livers and spleens of intravenously infected mice. The attenuated in vivo growth of the entire atp operon mutant was complemented by the insertion of the atp operon into the malXY pseudogene region. Following clearance of the attenuated mutants from the organs, mice were protected against challenge with the virulent wild type parent strain. We have shown that the F(0)F(1) ATPase is important for bacterial growth in vivo and that atp mutants are effective live attenuated vaccines against Salmonella infection.
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
authors.forename: H
authors.initials: H
authors.lastname: Northen
authors.forename: G K
authors.initials: GK
authors.lastname: Paterson
authors.forename: F
authors.initials: F
authors.lastname: Constantino-Casas
authors.forename: C E
authors.initials: CE
authors.lastname: Bryant
authors.forename: S
authors.initials: S
authors.lastname: Clare
authors.forename: P
authors.initials: P
authors.lastname: Mastroeni
authors.forename: S E
authors.initials: SE
authors.lastname: Peters
authors.forename: D J
authors.initials: DJ
authors.lastname: Maskell
mesh_terms: D000818:Animals; D025243:Bacterial Proton-Translocating ATPases / Q000235:genetics*; D015169:Colony Count, Microbial; D005260:Female; D017353:Gene Deletion; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D008099:Liver / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009876:Operon; D012481:Salmonella Infections, Animal / Q000382:microbiology; D022562:Salmonella Vaccines / Q000235:genetics* / Q000276:immunology*; D012486:Salmonella typhimurium / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D013154:Spleen / Q000382:microbiology; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014774:Virulence
chemical_list: D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated; D025243:Bacterial Proton-Translocating ATPases