[EFFECT OF EXTRACHROMOSOMAL ELEMENTS OF HEREDITY ON TOXIC PROPERTIES OF YERSINIA PESTIS].

AIM: Elucidation of the role of extrachromosomal elements of heredity in manifestations of toxic properties of Yersinia pestis. MATERIALS AND METHODS: The study was carried out in vac- cine strain Y pestis EV76 (pMT1, pCD1, pPCP1) and non-plasmid variants of vaccine EV76 (pMT1⁻, pCD1⁻, pPCP1⁻) and virulent 231 (pMT1⁻, pCD1⁻, pPCP1⁻) strains of Y pestis. Presence of functionally active form of lipopolysaccharide (LPS) in.the incubation medium of the bacteria was evaluated via toxicity of supernatant of Y pestis for intactanimals (infec- tion-toxic shock) and mice sensitized by D-GalN. RESULTS: 37°C cultures of Y pestis EV76 containing a full amount of plasmids were established to release LPS into the environment. Non-plasmid variants of both vaccine and virulent strains of Y.pestis pMT-, pCD1-, pPCP1- do not have this ability. Separation of LPS from cell wall was detected in live bacteria of plague infectious agent. This process is assumed to be coupled with translocation of proteins coded by pMT1, pCD 1, pPCP 1 plasmids from the cell into the environment. CONCLUSION: Functional inter-connection between extrachromosomal elements of heredity and toxic activity of Y pestis LPS is established for the first time.

[SPECIFICITY OF IMMUNE MODULATING EFFECT OF YERSINIA PESTIS ENDOTOXIN].

Literature and own data on mechanisms, of realization of lipopolysaccharide (LPS) toxic potential of Yersinia pestis in the conditions of a macroorganism are analyzed. 2 modifications of LPS are examined - temperature dependent changes of chemical structure of polymers and a change in their conformation under the effect of micro- and macroorganism factors. A special attention is paid to comparative study of toxic and immune modulating properties of the specified LPS forms. Both LPS forms are concluded to activate TLR4/MD2 receptor, inducing synthesis of 2 types of cytokines - pro-inflammatory and interferons. However, dominance of their signal pathways and cross-regulation of the transduced signal are mirrored, and as a result the initial form of LPS initiates interferon synthesis, and conformationally changed - pro-inflammatory cytokines. Results of the experiments are summarized in 2 schemes of signal transfer by TLR4/MD2 receptor under the effect of 2 forms of Y pestis LPS. Variations of cytokine-inducing properties of the initial and conformationally-altered forms of Y pestis LPS corresponds to the immune response of the organism at each stage of the infectious process: late inflammatory response by interferon type is characteristic for intracellular cycle of plague development, and pro-inflammatory cytokine hyper-production is observed at the terminal stage of infection-toxic shock.