title: A surface protease and the invasive character of plague.
abstract: A 9.5-kilobase plasmid of Yersinia pestis, the causative agent of plague, is required for high virulence when mice are inoculated with the bacterium by subcutaneous injection. Inactivation of the plasmid gene pla, which encodes a surface protease, increased the median lethal dose of the bacteria for mice by a millionfold. Moreover, cloned pla was sufficient to restore segregants lacking the entire pla-bearing plasmid to full virulence. Both pla+ strains injected subcutaneously and pla- mutants injected intravenously reached high titers in liver and spleen of infected mice, whereas pla- mutants injected subcutaneously failed to do so even though they establish a sustained local infection at the injection site. More inflammatory cells accumulated in lesions caused by the pla- mutants than in lesions produced by the pla+ parent. The Pla protease was shown to be a plasminogen activator with unusual kinetic properties. It can also cleave complement C3 at a specific site.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655.
authors.forename: O A
authors.initials: OA
authors.lastname: Sodeinde
authors.forename: Y V
authors.initials: YV
authors.lastname: Subrahmanyam
authors.forename: K
authors.initials: K
authors.lastname: Stark
authors.forename: T
authors.initials: T
authors.lastname: Quan
authors.forename: Y
authors.initials: Y
authors.lastname: Bao
authors.forename: J D
authors.initials: JD
authors.lastname: Goguen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins; D015169:Colony Count, Microbial; D004926:Escherichia coli / Q000201:enzymology; D005341:Fibrinolysin / Q000737:chemistry / Q000378:metabolism; D007275:Injections, Intravenous; D007700:Kinetics; D008099:Liver / Q000382:microbiology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010930:Plague / Q000382:microbiology; D010957:Plasmids; D010960:Plasminogen Activators / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D013154:Spleen / Q000382:microbiology; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D015010:Yersinia pestis / Q000201:enzymology* / Q000302:isolation & purification / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; C078140:Pla protease, Yersinia pestis; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator