[Immunomodulatory properties of 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate and search for its new derivatives]. / Immunomoduliatornye svoistva i poisk novykh proizvodnykh 2-C-Metil-D-éritriol-2,4-tsiklopirofosfata.

A strong immunomodulatory effect of 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEC) responsible for the survival of bacteria was shown on isolated macrophages and in experimental infections in mice (typhoid and tularemia). Derivatives of MEC were found by 1H-NMR spectroscopy under stress conditions in colorless mutants of the bacteria and isolated to be subsequently purified and used for modulation of the immune system of animals.

[Interaction of bacteria with mercuric compounds]. / Vzaimodeistvie bakterii s rtutnymi soedineniiami.

We investigated the interaction of mercuric compounds with the bacteria Corynebacterium ammoniagenes, Micrococcus luteus, and Mycobacterium smegmatus capable of producing hydroxylamines (R-NOH) and 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MECP), which are prone to form free radicals. The interaction of these substances with Hg2+ ions and their dynamics during the mercuric poisoning of bacteria was studied by EPR and NMR. Under stress conditions induced by lowering pH or generation of active oxygen species, the bacteria and, especially, their mutants with enhanced sensitivity to oxidative stress, were found to respond to exposure to 1-3 micrograms/ml HgCl2 and p-chloromercuribenzoate by a several-fold increase in their viability. The data obtained were interpreted in terms of the involvement of the sulfhydryl groups of bacterial surface proteins in this phenomenon. The interaction of bacteria with mercuric compounds may affect the pathogenesis of tuberculosis and other diseases.

[Relationship between the synthesis of a new stress response component and bacterial cell metabolism]. / Sviaz' sinteza novogo komponenta stressornoi reaktsii s metabolizmom bakterial'noi kletki.

Various stress factors (incubation with redox-cycling agents, ozonization, heat shock) that induced accumulation of 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEC) were also shown to induce various alterations of the phospholipid composition in three microbial species: Corynebacterium ammoniagenes, Micrococcus luteus, and Staphylococcus aureus. The influence of adding 10 carbohydrates to the growth medium on MEC accumulation by C. ammoniagenes cells was tested. Only glucose and mannose exerted a pronounced stimulatory effect on the MEC synthesis under oxidative stress. The target of oxidative attack whose transformation causes MEC synthesis is suggested to be located near or on the bacterial cytoplasmic membrane.

[Participation of 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate in reactions of bacteria on oxidative stress and their persistence in macrophages]. / Uchstie 2-C-metil-D-éritritol-2,4-tsiklopirofosfata v reaktsii bakterii na okislitel'nyi stress i v ikh persistentsii v makrofagakh.

In aerated medium, Corynebacterium ammoniagenes cells accumulate 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEC) during heat shock and in the presence of O2--generating compounds or ozone. The ability to accumulate MEC was genetically transformed from C. ammoniagenes to E. coli XL-1; transformed E. coli (2-31 clone) accumulates MEC in the presence of glucose and glucose oxidase (generation of H2O2) or benzylviologen (generation of O2-); the viability of transformed bacteria inside the murine peritoneal macrophages also significantly increases. However, model conditions of phagosomes of warm-blooded animals (NO + H2O2 + O2-) did not cause MEC accumulation by C. ammoniagenes but increased the formation of polyphosphate which can be due to selective oxidative aberration of biosynthetic processes. Growth rate of Acanthamoeba castellanii on solid medium with bacterial lawn was not significantly different in C. ammoniagenes, C. ammoniagenes with preaccumulated MEC, E. coli XL-1, and E. coli 2-31 and did not depend on the accumulation of MEC by bacteria. Unlike the recipient E. coli strain, the transformed 2-31 clone synthesizes two nonpolar lipids (Rf = = 0.85 and 0.75; TCL on Silufol in hexane) and carotinoid pigments; this can be due to changes in metabolic pathways of isopentenylpyrophosphate that can be a precursor of MEC biosynthesis. Thus, MEC is involved in bacterial responses to certain components of oxidative stress and in bacterial persistence inside the macrophages.