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K-2270

Application of probiotics in complex treatment of tuberculosis

Project Status: 3 Approved without Funding
Duration in months: 24 months

Objective

Project aim: an increase in efficiency of the treatment of the experimental tuberculosis by means of use probiotics in its complex treatment.

According to literature sources, tuberculosis is one of the leading human diseases in Kazakhstan [1]. Besides social, environmental and economic reasons, prevalence of tuberculosis is associated with emergence of forms of the disease that are resistant to the medications.

One of the ways to fight against antibiotic-resistant infectious diseases may be use of probiotics based on lactic acid bacteria and their metabolites for therapeutic and prophylactic reasons. Lactic acid bacteria are symbionts of the gastrointestinal tract and are harmless to humans and animals. They have therapeutic effect due to antimicrobial activity, immune system activation and normalization of intestinal microbial population. It is important that in relation to probiotics, resistant forms of pathobionts are not formed.

According to published data, lactic acid bacteria can be used for treatment of septic wounds and inflammatory diseases of the urogenital tract. Our research in 2000-2005 also confirmed high efficiency of the association of lactic acid and propionic acid bacteria for treatment of inflammatory diseases caused by purulent infection [2].

Thus, some strains of lactic acid bacteria and their associations can be used successfully, especially in complex treatment, in the struggle not only against intestinal infections, but also diseases localized outside the gastrointestinal tract. In such a case, there must be strains of lactobacilli, antagonistic to the agents of specific diseases that are resistant to the used antibiotics.

For the prevention and treatment of tuberculosis we made selection of lactic acid bacteria strains which had bactericidal activity against Micobacterium tuberculosis B5. The most active antagonists to the specified assay culture were Lactobacillus cellobiosus 7n and 20, Lactobacillus brevis 65n, В-3, Lactobacillus plantarum 22, 2b and 14d, Lactobacillus fermentum 27 and 127 with bactericidal activity, associations A and P were selected which differ in composition of lactic acid bacteria. Association A consists of lactic acid bacteria L. plantarum 2b and 14d, L. brevis В-3 and propionic acid bacteria Propionibacterium shermanii-15; association P consists of lactic acid bacteria L. plantarum 22 and L. fermentum 127. Strains resistant to the following anti-tuberculosis antibiotics at a concentration of 100 mkg/ml was determined - ethambutol, pyrazinamide, ofloxacin, ciprofloxacin, streptomycin, kanamycin, isoniazid, etc. Resistance to rifampicin was observed only at a concentration of 10 mkg/ml.

The above materials show promise for research in the development of new effective probiotics for complex treatment of tuberculosis.

For accomplishment of the objectives, it is planned:


1. To investigate the antibiotic activity of selected probiotics on the basis of associations A and P against the clinical strains Mycobacterium tuberculosis and their resistance to antibiotics, used for treatment.

2. To select combinations of probiotics and antibiotics having synergistic effect with respect to specific pathogens.


3. To perform the trials of drug on experimental animals.

4. To develop technological instructions for the production of selected probiotics.

The project will be attended by qualified professionals: microbiologists dealing with selection, breeding and studying of physiological and biochemical properties of lactic acid bacteria and having experience in development of probiotics of directed action; chemists who are familiar with methods of spectroscopy and chromatography of biologically active agents, veterinarians and physicians working in the field of multi drug resistant (MDR) tuberculosis treatment.

The project meets the objectives of non-proliferation as it enables scientists and engineers who worked previously for government contracts in the field of biological defense to redirect focus of their scientific interests and apply their accumulated experience to perform basic and applied researches related to solution of international scientific and technical problems in the field of biology, medicine and veterinary science for peaceful purposes, and create long-term prospects for productive activity within the international scientific community.

The work is designed for 2 years. The process of its implementation will include classical microbiological methods of selection and identification of lactic acid bacteria, genetic, molecular, biological and analytical methods focused on determination of exact systematic affiliation of the studied bacterial cultures; determination of antagonistic activity, capacity for adhesion, resistance to antibiotics, light and electron microscopy, UV and IR-spectrophotometry, thin-layer chromatography, gas chromatography with application of mass-selective det

Participating Institutions

LEADING

Institute of Micribiology and Virrology

PARTICIPATING

The Joint - Stock Company "Kazagroinnovation" Limited Liability Company "Kazakh Scientific-Research Veterinaty Institute" (LLP KazSRVI)

COLLABORATOR

Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie Ludwig-Maximilians-Universität München

COLLABORATOR

Rutgers University / Department of Biochemistry and Microbiology

COLLABORATOR

Kyorin University School of Medicine