title: Studies on the role of plasminogen activator in systemic infection by virulent Yersinia pestis strain C092.
abstract: Plasminogen activator is an outer membrane protease of Yersinia pestis encoded by the pla gene on plasmid pPst. Pla of the KIM-10 strain of Y. pestis appears to be required for the virulence from a subcutaneous (sc) but not an intraperitoneal (ip) or intravenous (iv) route of infection in mice. However, other strains of Y. pestis are highly virulent by the sc route yet lack pPst and pla. In this study, the pPst- Pestoides F strain was lethal to mice inoculated sc, with an LD50 (3 cfu), equal to that of C092, a virulent pPst+ strain. To analyse further the role of Pla in invasive infection, isogenic derivatives of C092, including one harboring pla with a frameshift mutation and another cured of pPst, were made. Although the ip LD50 of pPst- C092 and of the pla mutant were nearly identical to that of the wild type, the subcutaneous LD50 of the cured and mutant strains were 4 to 6 logs greater than that of wild type. Thus, pPst appears to be required for development of a lethal infection by some strains after sc inoculation but not after direct ip inoculation. Pla-associated virulence did not appear to be mediated by interference with the phagocyte chemoattractant C5a, as shown by the lack of correlation of C5a production with susceptibility to Y. pestis in C5a+ and C5a- congenic mice. In a footpad model of the early host response to subcutaneous infection, pPst- C092 proliferated at the subcutaneous injection site to a similar extent as did the wild type parent strain, and elicited a similarly large, local inflammatory response. However, the wild type was present at higher concentrations at more distant sites such as the popliteal lymph node and spleen.
authors.affiliation: Division of Bacteriology, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Welkos
authors.forename: A M
authors.initials: AM
authors.lastname: Friedlander
authors.forename: K J
authors.initials: KJ
authors.lastname: Davis
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D001426:Bacterial Proteins; D003001:Cloning, Molecular; D015936:Complement C5a / Q000172:deficiency; D004269:DNA, Bacterial / Q000235:genetics; D016368:Frameshift Mutation; D017353:Gene Deletion; D007928:Lethal Dose 50; D008198:Lymph Nodes / Q000382:microbiology; D051379:Mice; D008817:Mice, Mutant Strains; D010930:Plague / Q000209:etiology*; D010957:Plasmids; D010960:Plasminogen Activators / Q000096:biosynthesis / Q000235:genetics*; D017422:Sequence Analysis, DNA; D015010:Yersinia pestis / Q000235:genetics / Q000472:pathogenicity*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D015936:Complement C5a; C078140:Pla protease, Yersinia pestis; D010960:Plasminogen Activators