Background:Peroxide-producing lactobacilli provide protection from infection for the female reproductive tract. However, in vitro studies demonstrated that H2O2-produced by Lactobacillus is not the cause of inhibition of pathogens. It is not exactly known how H2O2-producing lactobacilli are involved in the protection of the vaginal environment.Objectives:This study aimed to evaluate the importance of the interaction between H2O2-producing lactobacilli and their host for the resistance of the vaginal biotope.Materials and Methods:In this study, we used vaginal lactobacilli (11 H2O2-roducing strains and 11 non-H2O2-producing strains). The influence of epithelial cells on the growth and antibacterial activity of lactobacilli were evaluated. The effects of lactobacilli on the antibacterial activity of the epithelial cells, muramidase and lactoferrin were also determined.Results:Vaginal epithelial cells stimulated the growth and antibacterial activity of H2O2-producing lactobacilli in a greater extent than that of the non-H2O2-producing lactobacilli. Mainly, the H2O2-producing lactobacilli were capable of increasing the activity of the host antimicrobial peptides (muramidase and lactoferrin) as well as the antibacterial activity of the epithelial cells.Conclusions:The involvement of the peroxide-producing lactobacilli in the protection of vagina was due to their ability to effectively interact with the host. This is expressed on one side to stimulate the growth and antagonistic activity of lactobacilli and on the other side to increase the antibacterial activity of the host defense factors (muramidase, lactoferrin and metabolites of epithelial cells).

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It was shown that IL-1β, IL-8, and IL-6 in concentrations similar to those in the vagina of healthy women stimulated the growth of normal microflora (Lactobacillus spp.) and suppressed the growth and biofilm production by S. aureus and E. coli. On the contrary, these cytokines in higher concentrations typical of vaginal dysbiosis suppressed normal microflora and stimulated the growth of opportunistic microorganisms. TGF-β1 in both doses produced a stimulating effects on study vaginal microsymbionts. It is hypothesized that pro-inflammatory cytokines serve as the molecules of interspecies communication coordinating the interactions of all components of the vaginal symbiotic system.

We studied as hydrogen peroxide, lactic acid, or surfactants from clinical isolates of vaginal lactobacilli and cell-free supernatants from probiotic strain LCR35 can influence on the sensitivity of opportunistic bacteria to antibiotics. We found that the most effective in increasing sensitivity to antibiotics were hydrogen peroxide and surfactants or their combination but no lactic acid. In some cases, the effect of the composition of hydrogen peroxide and surfactants was clearly higher than the sum of effects of these substances alone. With using of the supernatant of LCR35 was shown that the combination of surfactant and lactate has greater effect compared with surfactants alone. In concluding, metabolites of vaginal lactobacilli are suitable for the role of "antibiotic assistants" and it can help solve the problems the antibiotic resistance.

The phenomenon of microbial regulation of bacterial antagonism was studied using metabolites and cell walls of indicator microorganism culture as inductors. The algorithm of selection of stimulators of bacterial antagonistic activity is determined, experimental conditions are described, and methodological approach to stimulation of bacterial antagonistic activity is developed, which can be used for stimulation of probiotic antagonistic activity and for improving colonization resistance of the host organism during infection.