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The brucellosis is an actual zoonotic disease in many countries, Russia included. The complexity of individual prognosis of disease and choice of tactics of maintenance of patients is explained by heterogeneity of clinical manifestations of brucellosis and different rate of progression of organs pathology. Despite of low mortality, this pathology quite often results in disability of patient. The frequent transition of acute process into chronic one (40-60%), probability of development of primary chronic brucellosis determines interest of researchers to issues of immunopathogenesis of this disease. The article presents review of achievements in studies of polymorphism of genes of gamma-interferon in the given area.

Brucella pathogens are highly susceptible in vitro to pefloxacin, lomefloxacin, meropenem and azithromycin. High efficacy of these drugs was demonstrated for experimental brucellosis treatment, azithromycin being the most active. Meropenem and azithromycin implementation resulted in more rapid and full normalization of the bactericidial and energy systems of the experimental animals peripheral blood cells.

The possibility of preparing B. abortus vaccine strain 19-BA with multiresistance to antibiotics was shown. The strain was obtained by the spontaneous induction of resistance to rifampicin with the subsequent transformation of nonconjugative hybrid plasmid pOVI which, in addition to rifampicin resistance, governed the resistance of brucellae to tetracycline, doxycycline, ampicillin, and streptomycin. Experiments on guinea pigs demonstrated the immunization with both multiresistant vaccine strain GSA1 and B. abortus initial vaccine strain 19-BA.

In vitro activity of 13 antibiotics and drug preparations as well as some of their combinations was studied with respect to Brucella melitensis. It was shown that the strains of B. melitensis were sensitive to sisomicin, amikacin, gentamicin, cefotaxime, rifaprim +, nitroxoline and trimethoprim. Variations in the doxycycline sensitivity depending on the strain were observed. The strains of B. melitensis were resistant to cephalexin, phosphomycin, chinoxydine, dioxydine and oxolinic acid. Combinations of sisomicin and trimethoprim at a ratio of 1:10 and sisomicin and nitroxoline at a ratio of 1:2 had a summation effect.

The submicroscopic organization of Brucella cells in the process of L-transformation and reversion has been studied. As revealed in this study, at its initial stages L-transformation is accompanied by the loss of cell-wall peptidoglycan and by considerable polymorphism of Brucella cells. Further stages are characterized by the presence of a great number of closed annular membrane structures both in the cytoplasm and outside the cells. At late stages of L-transformation the destruction of the cytoplasm and the cells has been found to occur. In revertant cultures the restoration of the cell wall has been noted.

The possible use of the Unimicon-s nutrient medium for determination of antibiotic sensitivity of Brucella by the methods of serial dilutions in dishes and agar diffusion with paper disks was studied. Previously this method was not used in manipulations with Brucella. The results indicated that the dry Unimicon-s nutrient medium was applicable for determination of Brucella antibiotic sensitivity. It was shown that the agar diffusion method with the use of paper disks may be recommended for determination of antibiotic sensitivity of Brucella. The optimal time for recording the results of the laboratory assays is 48 hours.

Mutagenic activity of N-methyl-N'-nitro-N-nitrosoguanidine with respect to Brucella melitensis was studied. In the course of this study the method of obtaining auxotrophic brucella mutants was elaborated. Numerous assortiment of auxotrophic mutants of different types was obtained. In a number of cases the acquisition of auxotrophy was accompanied by profound changes of the strain, such as the changes in morphology of colonies, in the biochemical activity, in the capacity of agglutination and in the virulence.

The capacity of 216 Brucella strains to produce bacteriocins was studied. The strains were isolated from patients, farm animals, mouse-like rodents and food products in brucellosis foci of the Caucasus. The data on induction of brucellacin synthesis with methylrosanilinum chloride and screening of new indicator strains are presented. Brucellacin was isolated from 134 (62.1 per cent) cultures of Br. melitensis, Br. abortus, Br. suis and Br. ovis. Differences in the nature of the inhibition growth zones of Br. neotomae 325, an indicator culture obtained with the use of brucellacins from various Brucella species were noted. The brucellacin-producing cultures were detected under the effect of methylrosanilinum chloride among Br. abortus and Br. melitensis with an increase in the number of the bacteriocinogenic isolates and the size of the inhibition growth zones of the indicator culture. At the same time it was found that methylrosanilinum chloride suppressed the bacteriocinogenic properties of Br. suis and was indifferent with respect to the bacteriocinogenic properties of Br. ovis. Three indicator cultures, i.e. 14, 19 and 33 of Br. melitensis and one indicator culture, i.e. 718 of Br. ovis are recommended for identification of brucellacin.

Investigation of the properties of antibiotic-resistant variants obtained experimentally from various species of Brucella indicated that benzylpenicillin, ampicillin and ceporin induced significant changes in the main properties of Brucella, i.e. phagolysability, agglutinability, production of brucellacin and hydrogen sulfate, attitude to dyes. Only the nutrient requirements of Brucella did not change when it was grown on synthetic media which is of great importance for investigation of changed Brucella strains.

Optimal conditions for rapid assay of Brucella antibiotic sensitivity with the immunofluorescent method were developed. With this method high sensitivity of the main Brucella species to tetracycline, doxycycline and rifampicin was confirmed. It was found actually possible to use the immunofluorescent method for rapid assay of Brucella antibiotic sensitivity in practice.

The in vitro study of the possible formation of L-forms of Brucella under the effect of tetracycline, streptomycin, rifampicin or their combinations with penicillin showed that passages of various Brucella species on media containing increasing concentrations of the antibiotics resulted in insignificant morphological changes in the cells. Passages of the same cultures on media containing combinations of the above antibiotics with penicillin resulted in more significant changes in the cell morphology, up to formation of spheroplasts. No L-transformation was observed under the experimental conditions.

Irrespective of their geographical origin the cultures of Br. ovis are highly sensitive to tetracycline and streptomycin. The bactericidal concentrations of tetracycline for 86.6 per cent of the strains and streptomycin for 93.20 per cent of the strains were 0.02--0.04 and 0.1--0.4 gamma/ml respectively. The bactericidal effect of morphocycline, kanamycin, benzyl-penicillin, lincomycin and monomycin was less pronounced. Polymyxin M had no bactericidal effect on the Brucella even in concentrations of 200 gamma/ml. Antibiotic sensitivity of S-subcultures of Br. ovis and the initial R-variants was studied comparatively. It was found that genetically related S-subcultures of Br. ovis were more resistant to the antibiotics than the initial R-strains.