A Yersinia pestis guaBA mutant is attenuated in virulence and provides protection against plague in a mouse model of infection.
There is a need to develop effective countermeasures for Yersinia pestis, the etiologic agent of plague and a potential bioterrorism agent. Salmonella and Shigella spp. deleted in the guaBA genes involved in guanine biosynthesis have been shown to be attenuated in vivo. In this study, we sought to determine whether deletion of the guaBA operon would render Y. pestis auxotrophic for guanine and avirulent; such a strain could serve as a live attenuated plague vaccine candidate. A Y. pestis guaBA mutant was generated by specific deletion of a segment of the guaBA operon, producing a guanine auxotroph that was highly attenuated in a mouse model of Y. pestis infection. Furthermore, mice vaccinated with a single dose of 7x10(4)CFU via the intravenous route were fully protected against subsequent lethal challenge with the Y. pestis parental strain. These findings identify guaBA as a target for deletion to generate a live attenuated plague vaccine.
Oyston
Petra C F
PC
Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, United Kingdom.
Mellado-Sanchez
Gabriela
G
Pasetti
Marcela F
MF
Nataro
James P
JP
Titball
Richard W
RW
Atkins
Helen S
HS
D000818:Animals; D005260:Female; D017353:Gene Deletion; D006147:Guanine / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009876:Operon; D010930:Plague / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control*; D010931:Plague Vaccine / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics; D015010:Yersinia pestis / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*
D010931:Plague Vaccine; D014613:Vaccines, Attenuated; D037521:Virulence Factors; D006147:Guanine