title: Deletion of the Bacillus anthracis capB homologue in Francisella tularensis subspecies tularensis generates an attenuated strain that protects mice against virulent tularaemia.
abstract: As there is currently no licensed vaccine against Francisella tularensis, the causative agent of tularaemia, the bacterium is an agent of concern as a potential bioweapon. Although F. tularensis has a low infectious dose and high associated mortality, it possesses few classical virulence factors. An analysis of the F. tularensis subspecies tularensis genome sequence has revealed the presence of a region containing genes with low sequence homology to part of the capBCADE operon of Bacillus anthracis. We have generated an isogenic capB mutant of F. tularensis subspecies tularensis SchuS4 and shown it to be attenuated. Furthermore, using BALB/c mice, we have demonstrated that this capB strain affords protection against significant homologous challenge with the wild-type strain. These data have important implications for the development of a defined and efficacious tularaemia vaccine.
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Michell
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Dean
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Jim E
authors.initials: JE
authors.lastname: Eyles
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Margaret Gill
authors.initials: MG
authors.lastname: Hartley
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Waters
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Joann L
authors.initials: JL
authors.lastname: Prior
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Petra C F
authors.initials: PCF
authors.lastname: Oyston
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001408:Bacillus anthracis / Q000235:genetics; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D019295:Computational Biology; D005260:Female; D005604:Francisella tularensis / Q000235:genetics*; D005798:Genes, Bacterial; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009876:Operon; D016415:Sequence Alignment; D017384:Sequence Deletion; D017385:Sequence Homology; D016019:Survival Analysis; D014406:Tularemia / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated; D037521:Virulence Factors