The dissertation is devoted to the study of the biological properties of staphylococci in biofilms and the possibilities of targeting them to inhibit the processes of biofilm formation. Analysis of the spreading of the ability to form a biofilm among the strains of staphylococci, isolated from the reproductive tract of women, upper respiratory tract, skin, gastrointestinal tract (intestine and oral cavity) of healthy individuals and
persons with pathological manifestations, and among the strains isolated from abiotic surfaces, showed that the frequency of detection of staphylococci in these biotopes during pathological processes is not less than 75 %. Among staphylococcal strains S. aureus (46 % and more) and S. epidermidis (38 % and more) were the dominant species that depends on the biotope. The ability to form a biofilm coincided with sensitivity to phage 47. Among the differences in the sensitivity to antibiotics, it is also possible to indicate that for strains of S. aureus the drugs that inhibit the synthesis of protein and cell wall are more effective, and for the strains of S. epidermidis the maximum sensitivity to fluoroquinolones has been determined, which indicates the presence of certain patterns of formation of resistance of staphylococci of different species. The study of the catabolic characteristics of film forming strains showed that the intensity of accumulation of lactate was significantly higher in anaerobic conditions,
as evidenced by a higher rate of Pasteur effect, which for film-forming strains was 19 %. It was found that the activity of regulatory enzymes of glycolysis (phosphofructokinase, aldolase of fructose-1,6-diphosphate and pyruvate kinase) of studied film forming strains of staphylococci was lower than the control group for 28.2 %, 13.3 % and 26.9 %, respectively, compared with the staphylococcal strains isolated from the vagina of women without dysbiosis of reproductive tract. It was determined that the maximal cell growth in the biofilm of strains of S. aureus and S. epidermidis was observed in the first 72 h of incubation without the replacement of the nutrient medium when the number of cells reached to values above 8 lg CFU / ml. At the same time, the highest intensity of growth of the culture of S. aureus occurred during the first 24 h of cultivation, when the growth was observed more than 250 times, and for S. epidermidis the growth rates were the highest in the period from 24 to 48 h. The maximal amount of cells was fixed in 72-hour films: for S. aureus, it was 8.96±7.67 lg CFU / ml, while in the film of S. epidermidis – 9.45 ± 8.84 that indicate the predominant development of the matrix in the film S. aureus and cellular mass in the film of S. epidermidis. A distinctive feature of film growth in the strains of studied strains of staphylococci was that their growth rates differed significantly even under cultivation under the same conditions. It was determined that in the intact biofilms of S. aureus and S. epidermidis the dynamics of development was as follows: for the first the maximal increase of the number of cells was noted up to 24 h incubation, and for second – from 24 to 48 h. The maximal number of cells during cultivation without changing of the nutrient medium was 8 lg CFU / ml and more, and when the medium
was replaced and the experiments were prolonged to 120 h, the number of cells increased more than 105 times. For strains of S. aureus and S. epidermidis it has been shown that the maximal increase occurred under conditions of neutral pH, as well as the growth rates were closer to the maximum when the film was grown at pH 6 and 8. When glucose, sucrose, lactose or galactose added to the medium at a concentration of 2.5 % or more the strong inhibitory effect on the formation of the biofilm was noted. The ions of zinc and magnesium lead to the decrease of the number of cells and the biofilm formation index. The addition of phages to already formed films also had a depressant effect, resulting in a decrease of more than 84 times when applied to daytime films and more than 37 times when applied to older films compared to intact ones. The maximal effect of bacteriophages was observed during adding to 48 h film the Staphylococcal bacteriophage liquid for a 24 h film. On in vivo model of vaginal dysbiosis was shown that the most effective
correction scheme was a complex of two probiotics – bisporine and vagilac, the result of action of it was the reduction of the amount of lactobacilli with simultaneously decreasing of the number of opportunistic microorganisms. Index of ratio of aerobic: anaerobes increased and were close to those determined in the control group of healthy animals, which in fact indicated the renovation of microbiota of the vagina.
