Studies on the role of plasminogen activator in systemic infection by virulentYersinia pestisstrain C092

Abstract

Plasminogen activator is an outer membrane protease ofYersinia pestisencoded by theplagene on plasmid pPst. Pla of the KIM-10 strain ofY. pestisappears 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 ofY. pestisare highly virulent by the sc route yet lack pPst andpla. 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 harboringplawith a frameshift mutation and another cured of pPst, were made. Although the ip LD50of pPst- C092 and of theplamutant were nearly identical to that of the wild type, the subcutaneous LD50of 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 toY. pestisin 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.