title: A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague.
abstract: We determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virulence of all Y. pestis strains was compared in a mouse model for pneumonic plague. The presence of all known virulence genes correlated completely with virulence in the Balb/c mouse model. Strains which lacked HmsF initially exhibited visible signs of disease whereas all other strains (except wild-type strains) did not exhibit any disease signs. Forty-eight hours post-infection, mice which had received HmsF(-) strains regained body mass and were able to control infection; those infected with strains possessing a full complement of virulence genes suffered from fatal disease. The bacterial loads observed in the lung and other tissues reflected the observed clinical signs as did the cytokine changes measured in these animals. We can conclude that all known virulence genes are required for the establishment of pneumonic plague in mammalian animal models, the role of HmsF being of particular importance in disease progression.
authors.affiliation: TNO Defence, Security and Safety, 2280 AA, Rijswijk, the Netherlands. w.kaman@erasmusmc.nl
authors.forename: W E
authors.initials: WE
authors.lastname: Kaman
authors.forename: S
authors.initials: S
authors.lastname: Hawkey
authors.forename: D
authors.initials: D
authors.lastname: van der Kleij
authors.forename: M P
authors.initials: MP
authors.lastname: Broekhuijsen
authors.forename: N J
authors.initials: NJ
authors.lastname: Silman
authors.forename: F J
authors.initials: FJ
authors.lastname: Bikker
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001835:Body Weight; D016207:Cytokines / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D005798:Genes, Bacterial; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010930:Plague / Q000382:microbiology* / Q000401:mortality / Q000473:pathology*; D010957:Plasmids / Q000032:analysis; D016133:Polymerase Chain Reaction; D012376:Rodent Diseases / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*; D015010:Yersinia pestis / Q000235:genetics / Q000472:pathogenicity*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines; D004269:DNA, Bacterial; C082669:HmsF protein, Yersinia pestis; D037521:Virulence Factors