title: A Yersinia pestis YscN ATPase mutant functions as a live attenuated vaccine against bubonic plague in mice.
abstract: Yersinia pestis is the causative agent responsible for bubonic and pneumonic plague. The bacterium uses the pLcr plasmid-encoded type III secretion system to deliver virulence factors into host cells. Delivery requires ATP hydrolysis by the YscN ATPase encoded by the yscN gene also on pLcr. A yscN mutant was constructed in the fully virulent CO92 strain containing a nonpolar, in-frame internal deletion within the gene. We demonstrate that CO92 with a yscN mutation was not able to secrete the LcrV protein (V-Antigen) and attenuated in a subcutaneous model of plague demonstrating that the YscN ATPase was essential for virulence. However, if the yscN mutant was complemented with a functional yscN gene in trans, virulence was restored. To evaluate the mutant as a live vaccine, Swiss-Webster mice were vaccinated twice with the ΔyscN mutant at varying doses and were protected against bubonic plague in a dose-dependent manner. Antibodies to F1 capsule but not to LcrV were detected in sera from the vaccinated mice. These preliminary results suggest a proof-of-concept for an attenuated, genetically engineered, live vaccine effective against bubonic plague.
authors.affiliation: Division of Bacteriology, US Army Medical Research Institute of Infectious Diseases, Ft. Detrick, MD, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Bozue
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Cote
authors.forename: Wendy
authors.initials: W
authors.lastname: Webster
authors.forename: Anthony
authors.initials: A
authors.lastname: Bassett
authors.forename: Steven
authors.initials: S
authors.lastname: Tobery
authors.forename: Stephen
authors.initials: S
authors.lastname: Little
authors.forename: Wieslaw
authors.initials: W
authors.lastname: Swietnicki
mesh_terms: D000251:Adenosine Triphosphatases / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D005816:Genetic Complementation Test; D051379:Mice; D010930:Plague / Q000276:immunology / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D017384:Sequence Deletion; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D037521:Virulence Factors / Q000172:deficiency / Q000235:genetics; D015010:Yersinia pestis / Q000201:enzymology* / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D004269:DNA, Bacterial; D010931:Plague Vaccine; D014613:Vaccines, Attenuated; D037521:Virulence Factors; D000251:Adenosine Triphosphatases; C086388:YscN protein, Yersinia