[THE ACTUAL APPROACHES TO PROBLEM OF IMPORT SUBSTITUTION IN TH FIELD OF PRODUCTION GROWTH MEDIUM].

The import substitution becomes one of strategic tasks of Russian economy as a result of imposition of economic sanctions on part of the USA, EU countries, Japan and number of other states. The development of structure and technology of production of national import substituted growth mediums permits satisfying needs of laboratory service of Russia inactive storage and to secure appropriate response to occurring challenges and new biological menaces and support bio-security of state at proper level. The presented data concerning substantiation of nomenclature of growth mediums and transport system permit satisfying in fullness the needs of clinical and sanitary microbiology in growth mediums of national production and to give up of import deliveries without decreasing of quality of microbiological studies.

[Designing of laboratories is crucial for the management of biorisks in the work with pathogenic biological agents].

Currently in the Russian Federation there is planned the reconstruction and construction of new facilities tailored for the work with pathogenic biological agents of I-II pathogenicity groups, with bearing in mind the modern level of the development of equipment and technologies technological. However, in Russia there is no specialized institutions for the designing of such facilities. There were developed "Guidelines for the designing of objects of the Medical Sanitary Unit No164, tailored for the work with pathogenic biological agents of I-II pathogenicity groups", in which there were taken into account the requirements of modern Russian regulations in the field of biosafety air purification, fire safety.

[Biosafety in the study of samples of extraterrestrial origin by an example of preparation for the "Phobos-Grunt" mission].

The necessity of microbial studying the soil from Phobos and terrestrial biological objects, which were for a long time in deep space and may represent a biological hazard has been shown. Developed medical and technical requirements for laboratories comply with Russian regulations and recommendations of international instruments for the ensuring of biosafety on the basis of process (continuous) biorisk management.

[Perspectives of creation of vaccines against tick bite for nonspecific prophylaxis of vector borne diseases].

Prophylaxis of infectious diseases transferred by ticks is an important problem of contemporary medicine. One of the perspective approaches to solve this problem is the creation of vaccines against tickbite (anti-tickvaccines). Contemporary methods of the control of infectious diseases transferred by ticks are described in the review. Features of naturally and artificially acquired immunity against ticks are examined. Candidate tick antigens for the construction of vaccines against genus Ixodes tick bite are described. Perspectives of use of anti-tick vaccines against tick vector borne diseases are evaluated.

[Antimicrobial activity of bacteriocin S760 produced by Enterococcus faecium strain LWP760].

Antimicrobial activity of bacteriocin S760 (enterocin) produced by Enterococcusfaecium strain LWP760 was studied. Bacteriocin S760 is a cationic, hydrophobic, and heat stable peptide with the molecular weight of 5.5 kDa and pl of 9.8. Enterocin S760 is shown to inhibit in vitro the growth both of sensitive and resistant to antibacterials gramnegative and grampositive bacteria of 25 species. MICs of the bacteriocin S760 vary between 0.05-1.6 mg/l for Escherichia coli 0157:H117, Salmonella typhimurium, Salmonella enteritidis, Campylobacter jejuni, Yersinia enterocolitica, Yersinia pseudotuberculosis, Listeria monocytogenes and Clostridium perfringens, that are main food-borne pathogens, and from 0.4-1.6 mg/l for Streptococcus pyogenes, Streptococcus pneumoniae and Corynebacterium diphteriae. It is also active against antibioticresistant strains of Staphylococcus aureus, Enterobacter cloacae, Acinetobacter baumannii (with MICs of 0.05-3 mg/l), Klebsiella pneumoniae (with MICs of 6 mg/l), Pseudomonas aeruginosa (with MICs of 0.4-25 mg/1), as well against fungi belonging to species of Candida albicans, Candida krusei and Aspergillus niger (with MICs of 0.1-0.2 mg/l). Enterocin S760 is a novel antimicrobial agents useful in medicine, veterinary and food industry.

[Efficacy of enterocin S760 in treatment of mice with anthrax infection due to Bacillus anthracis M-71].

The therapeutic efficacy of enterocin S760, a broad spectrum antimicrobial peptide produced by Enterococcus faecium LWP760 was tested on mice infected with Bacillus anthracis M-71 to induce anthrax (second Tsenkovsky's vaccine). Intraperitoneal four-, two- or one-fold administration of the peptide in a dose of 25 mg/kg for 10 days for prophylactic (1 hour after the contamination) and therapeutic (24 hours after the contamination) purposes prevented or cured the infection in 90-100% of the mice versus the 100-percent lethality in the control (untreated animals). The antimicrobial activity of enterocin S760 against B. anthracis M-71 in vivo correlated with activity in vitro. Enterocin S760 is considered a novel promising antimicrobial for the treatment of grampositive and gramnegative infections.

[Use of enterocin S760 for prevention and treatment of experimental Salmonella infection in mice].

AIM: To demonstrate treatment efficacy of bacteriocin S760 synthesized by Enterococcus faecium 760 for septic Salmonella infection in mice. MATERIALS AND METHODS: One hundred mice, which were intraperitoneally inoculated with 100 LD50 of Salmonella enteritidis strain 92 Rif(r), received bacteriocin 1 hour (prevention) or 48 hours (treatment) after inoculation in doses 25, 50, or 100 mg/kg every 6 hours during 5 or 10 days. RESULTS: Use of peptide S760 for prophylaxis in dose 50 mg/kg during 10 days prevented lethal infection in 100% of animals, whereas its use for treatment cured 70% of animals with generalized salmonellosis. Shortening of treatment course from 10 to 5 days and reducing dose of bacteriocin led to less pronounced treatment effect but in all animals it was expressed by increase of mean length of life compared to control (not treated). CONCLUSION: Obtained results demonstrated high treatment efficacy of bacteriocin S760 during septic salmonellosis and perspectives of its use in medicine and animal health.

[Genetic determinants of antibacterial resistance among nosocomial Escherichia coli, Klebsiella spp., and Enterobacter spp. isolates collected in Russia within 2003-2007].

Nosocomial bacterial isolates collected within 2003-2004 (n=411) and 2005-2007 (n=422) were highly resistant to cephalosporins III-IV and antibacterials of other groups (aminoglycosides, fluoroquinolons, chloramphenicol, and co-trimoxazole). Genes encoding TEM, SHV, CTX-M, OXA-2, and AmpC types of beta-lactamases (BLs) in the E. coli, Klebsiella spp., and Enterobacter spp. isolates were detected using polymerase chain reaction (PCR). Prevalent CTX-M-type BLs were detected in 85% of the E. coli, 87% of the Klebsiella spp., and 38% of the Enterobacter spp. isolates of the first strain collection and in 94% of the E. coli, 91% of the Klebsiella spp., and 38% of the Enterobacter spp. isolates of the second one. Genes belonging to three subtypes of blacTx-M genes were identified: bla(CTX-M-1) (228 bla(CTX-M-15) and six bla(CTX-M-3) of the first strain collection; 275 bla(CTX-M-15), three bla(CTX-M-3), and one bla(CTX-M-22) of the second one), bla(CTX-M-2) (one bla(CTX-M-5) of the first strain collection and one bla(CTX-M-2) of the second one), bla(CTX-M-9) (17 bla(CTX-M-14) and one bla(CTX-M-9) of the first strain collection; seven bla(CTX-M-14) and one bla(CTX-M-9) of the second one). Three isolates of the first strain collection and one isolate of the second one carried two genes belonging to two different subtypes, i.e., bla(CTX-M-15) and bla(CTX-M-14) simultaneously. The bacterial isolates had high levels of associative resistance to ciprofloxacin, co-trimoxazole, gentamicin, amikacin, and chloramphenicol associated with the resistance gene cassettes aadA1, aadA2, aadA5, aadB, aacA4, aac(6')Ib; dfrA1, dfrA5, dfrA12, dfrA17, cmlA1, ereA2, and catB8 in the class 1 integrons and the resistance gene cassettes dfrA1, sat1, and aadA1 in the class 2 integrons.

[Characteristics of the immune response to the lethal toxin of Bacillus anthracis].

We and other authors have recently shown that the pattern of the immune response to components of anthrax, the Bacillus anthracis lethal toxin, is complex. In addition to neutralizing antibodies, the antitoxin antibody pool contains antibodies enhancing the toxin lethal action. We mapped the epitopes in the protective antigen that are responsible for the induction of both antibody types. In this study, we obtained new data on the cytotoxicity of the B. anthracis lethal toxin toward the J774 A.1 cell line in the presence of monoclonal antibodies to various domains of the protective antigen and the lethal factor. The role of the Fc fragment of immunoglobulins in enhancing the lethal toxin action was shown. These results may serve as a basis for the development of a new generation vaccine for anthrax.

[Genetic and immunochemical study of Legionella strains isolated in Sverdlovsk region].

Two strains of Legionella isolated from patient and hot water supply system during outbreak in Sverdlovsk region in 2007 were studied. Using genetic analysis methods (genes sequencing, VNTR-typing and PCR-based study of omp 28 gene), it was shown that tested strains are pathogenic but do not belong to one genetic group and epidemic cluster. Performed immunochemical analysis confirmed that both isolated strains belong to Legionella serogroup 1.

[Disinfectants and main sanitary and preventive measures for protection of ventilation and air-conditioning systems from Legionella contamination].

The study was devoted to selection and assessment of disinfecting preparations for prevention of contamination by Legionella. Using system of criteria for quality assessment of disinfectants, seven newdomestic ones belonging to quaternary ammonium compounds class or to oxygen-containing preparations and designed for disinfecting of air-conditioning and ventilation systems were selected. Antibacterial and disinfecting activities of working solutions of disinfectants were tested in laboratory on the test-surfaces and test-objects of premises' air-conditioning and ventilation systems contaminated with Legionella. High antimicrobial and disinfecting activity of new preparations "Dezactiv-M", "ExtraDez", "Emital-Garant", "Aquasept Plus", "Samarovka", "Freesept", and "Ecobreeze Oxy" during their exposure on objects and materials contaminated with Legionella was shown. Main sanitary and preventive measures for defending of air-conditioning and ventilation systems from contamination by Legionella species were presented.

[Evaluation of immunobiological activity of Francisella tularensis C-complex preparations as promising component of subunit vaccines].

Data on influence of Francisella tularensis C-complex preparations on formation of immunity against tularemia are presented. Study of cellular immunity characteristics as well as dynamics of antibody response was carried out on white mice and guinea pigs models. Absence of toxicity, pyrogenicity, and negative effects on immunocompetent cells in combination with protective activity points to possibility of use the C-complex as a component of a subunit vaccine.

[Anti-rabies immunoglobulin preparation based on F(ab')2 fragments].

Technology of manufacturing of new anti-rabies immunoglobulin preparation based on F(ab')2 fragments has been developed. This preparation is characterized by low reactogenicity, increased virus-neutralizing activity and stability.

[The properties of the cellular surface of Yersinia pestis strain EV and its achromogenic variants]. / Svoistva kletochnoi poverkhnosti shtamma Yersinia pestis EV i ego akhromogennykh variantov.

The comparative study of the properties of the surface of vaccine strain Y. pestis EV and its achromogenic variants (AV) differing from the initial strain by decreased immunogenicity and by the morphology of colonies, has been made. The achromogenicity of Y. pestis colonies has been shown to correlate with the loss of the outer membrane protein with a molecular weight 22 kD. The synthesis of this protein is determined by chromosomal genes. AV have been found to have different sensitivity to bacteriophages. The analysis of the electrokinetic potential of Y. pestis EV and its AV has revealed that in the latter have surface charge is considerably greater (1.4- to 1.5-fold). As shown in this study, the hemagglutinating activity of AV with respect to red blood cells of humans with blood group I (O) and guinea pigs is decreased by 1-2 orders and these strains do not agglutinate with sheep red blood cells. The low activity of the initial stage of the phagocytosis of AV by mouse macrophages has been shown. The possible role of the 22 kD proteins as an adhesion factor is discussed.