Pathogenetic Value of pVM82 Plasmid of Yersinia Pseudotuberculosis, Causative Agent of Far Eastern Scarlet-Like Fever

Abstract

The Far Eastern scarlet-like fever (FESLF) is the clinical-epidemic manifestation of pseudotuberculosis infection in humans is associated with a specific clonal lineage of the causative agent. Purpose of the study: to determine the pathogenetic value of the pVM82 plasmid of the FESLF causative agent, on the basis of a comparative analysis of the innate immunity cells metabolic activity and peculiarities of the inflammatory reaction during experimental infection, caused by different plasmid types of Yersinia pseudotuberculosis. Materials and Methods. The following Y. pseudotuberculosis plasmid types were used for the infection of mice: (1) H-5015 T+ strain (82+:48+) containing two plasmids pVM82 and pYV; (2) H-5015 T– strain (82+:48–) containing single pVM82 plasmid; (3) H-5013 T+ strain (48+) containing single pYV plasmid; (4) H-5013 T– plasmid-free strain (82–:48–). Peritoneal exudate cells and samples of liver, spleen and mesenteric lymph nodes were taken from infected animals at 1, 3, 5 and 7 days post infection. The functional state of the innate immunity cells was assessed by the activity of lactate dehydrogenase (LDH) and by the level of nitric oxide (NO) metabolites. The samples of target organs were embedded in paraffin, sections were stained with hematoxylin and eosin. Results. It was found that only Y. pseudotuberculosis strains containing pVM82 plasmid had a stimulating effect the innate immunity cells. The more pronounced increase in the LDH activity, an oxygen-dependent metabolism enzyme, and the level of NO metabolites occurred in response to infection of cells with bacteria containing single pVM82 plasmid, compared with plasmid type containing additional plasmid virulence pYV. In experimental animals infected with plasmid type pYV–: pVM82+ of Y. pseudotuberculosis, the disease pathology usually manifested less acute inflammation with a predominance of mononuclear cells and minor pathogen-associated destructive changes in organs. The mortality in animals infected with Y. pseudotuberculosis strains containing plasmid pVM82 (plasmid types 82+:48+ and 82+:48–) was lower compared to a strain carrying only the virulence plasmid pYV (plasmid type 48+),—40, 30 and 80%, respectively. Conclusions. Thus, the pVM82 plasmid of Y. pseudotuberculosis determined the effective immune defense of organism, mainly through nitroxide-dependent bactericidal mechanisms of innate immunity cells. Moreover, the restriction of a generalized inflammatory reaction and induction of granulomatous inflammation were associated with this plasmid.