Deletion of the Bacillus anthracis capB homologue in Francisella tularensis subspecies tularensis generates an attenuated strain that protects mice against virulent tularaemia.
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.
Michell
Stephen L
SL
Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Dean
Rachel E
RE
Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Eyles
Jim E
JE
Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Hartley
Margaret Gill
MG
Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Waters
Emma
E
Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Prior
Joann L
JL
Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Titball
Richard W
RW
Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Oyston
Petra C F
PCF
Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
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*
D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated; D037521:Virulence Factors