Simulation of Bubonic Plague in BSL-2 Laboratory

Abstract

The causative agent of plague, Yersinia pestis, is classified as pathogenicity (hazard) group I agent, which means that the work with “wild type” strains should be carried out in BSL-3 facilities. Y. pestis EV NIIEG is a Δpgm strain, allowing experimental studies to be carried out in BSL-2 laboratories. However, the disease and its progression elicited by such strain do not entirely mirror the infection observed with fully virulent strains. Residual virulence of Y. pestis EV NIIEG strain for mice can be increased under in vivo iron supplementation. The aim of the study was to optimize methodological approaches to modeling experimental plague in laboratory animals following administration of attenuated Δpgm Y. pestis strains with iron dextran. Materials and methods. Simulation of plague infection in outbred mice was carried out through subcutaneous inoculation of Y. pestis EV NIIEG strain with iron dextran supplementation. The animal condition was assessed on a daily basis. In the course of the experiment, the pathological presentation and bacterial content in organs of mice were evaluated. Results and discussion. Mice inoculated subcutaneously with Y. pestis EV NIIEG strain in the presence of iron dextran developed a bubonic plague that resulted in lethal outcome with pathological changes of internal organs, characteristic of plague infection. In case of daily administration of iron, LD50 of Y. pestis EV NNIEG strain for the mice significantly exceeded the same one with a single injection. Differences in the survival rate among animals in the groups with a single and multiple administration of iron compared to the control group were statistically valid. Thus, attenuated Δpgm Y. pestis strains in the presence of iron dextran can be used to model experimental plague in mice with marked pathological changes and lethality in BSL-2 laboratories.