Purpose of the Project. Within the Project, it is planned to carry out screening of actinomycetes isolated from the extreme ecosystems of Kazakhstan, and studies on activity of produced by them antibiotics against causative agents of tuberculosis and other life-threatening diseases.
State of affairs in the research area. The problem of the efficiency of treatment for tuberculosis and other life-threatening diseases has become particularly urgent due to the increasing all over the world morbidity level and wide spread of drug-resistant pathogens. In the treatment of these infections, it is important to develop new drugs by screening of new natural molecules or chemical modification of the known structures. In recent years, in screening programs a preference is given to studying insufficiently known extreme microbial habitats where of it is most probably to obtain new unique antibiotics. Studies on antibiotics produced by extremophilic actinomycetes from ecosystems of Kazakhstan are promising for the discovery of new natural drugs against pathogenic agents that cause socially significant diseases. Study on the antimicrobial properties was carried out in 2,500 strains of actinomycetes isolated from extreme ecosystems of Kazakhstan (salt marshes, solonetses, solods, takyrs, clayey and sandy deserts, bitter-salt lakes) under neutral and alternative (pH 9.0; NaCl 5.0%) conditions for isolation. 550 strains of extremophilic actinomycetes have been isolated which are active against gram-positive test microorganisms (MRSA, Mycobacterium spp.). The obtained strains of extremophilic actinomycetes form antibiotics in neutral and (or) salt and alkaline medium are producers of promising to further studying drug compounds.
Impact of the proposed Project on the progress in this area. As a result of successful implementation of the Project, the new natural antibiotics will be produced from extremophilic actinomycetes of Kazakhstan, with activity against causative agents of socially significant infections. Commercial value of new antibiotics lies in the possibility of their use in medicine for the treatment of diseases caused by pathogens causing life-threatening infections (tuberculosis, quarantine and zoonotic infections) with multiple drug resistance.
Competence of the Project participants in this area. To carry out collective work on the Project, the research staff of the Institute of Microbiology and Virology, MES RK, M. Aykimbaev Kazakh Scientific Center for Quarantine and Zoonotic Diseases, MNE RK (and invited from other research establishments) have the necessary qualifications and experience in the study of antibiotic substances, as evidenced by numerous publications in the national and foreign editions. The selected publications of the Project participants are presented in Section II.
Expected Results and Their Application. Antagonistic activity of extremophilic actinomycetes against strains belonging to the genera Mycobacterium, Staphylococcus, Escherichia will be studied. Extremophilic actinomycetes highly active against clinical strains of microorganisms will be selected. Optimal conditions for biosynthesis and isolation of promising antibiotics will be selected. Activity of new antibiotics against pathogenic strains of life-threatening infection pathogens will be studied. Activity of new antibiotics against drug-resistant pathogenic agents of life-threatening infections will be studied. Chemical identification of new promising antibiotics will be carried out. Taxonomic properties of producers of new promising antibiotics will be studied and their identification by methods of genetic analysis carried out.
Meeting ISTC Goals and Objectives. The goals of the proposed project comply with the activity and purposes of ISTC for strengthening international collaboration and integrating the CIS scientists into the world scientific community. Conducting the research within the project allows the scientists, primarily those dealing with biological weapons, to re-orient their activity to solving the problems of health care and environmental protection.
Data on the amount of work. The following main activities will be carried out within the Project:
- studying antagonistic activity of extremophilic actinomycetes isolated from ecosystems of Kazakhstan under neutral and alternative conditions (salinity, pH) against laboratory strains belonging to the genera Mycobacterium, Staphylococcus, Escherichia;
- selecting extremophilic actinomycetes highly active against clinical strains of gram-positive and gram-negative infectious pathogens;
- selecting optimal conditions for biosynthesis of promising antibiotics produced by extremophilic actinomycetes;
- selecting optimal conditions for isolation of promising antibiotics produced by extremophilic actinomycetes;
- studying activity of new antibiotics against strains of life-threatening infection pathogens (tuberculosis, quarantine and zoogenous infections);
- studying activity of new antibiotics against drug-resistant pathogenic agents of life-threatening infections;
- studying chemical nature of new promising antibiotics;
- studying taxonomic properties of extremophilic actinomycetes - producers of new antibiotics and their identifying by methods for genetic analysis.
Role of foreign collaborators. Staff of the University of the South Florida College of Public Health, Dr Boo Kwa, Head of the Health Department, and Dr. Azliati Azizan, his assistant, will collaborate on this Project. For a long time, between the Project participants and collaborators, the information exchange is being conducted in studying antimicrobial compounds produced by actinomycetes from Kazakhstan. The joint publications in rating editions and reports at the international conferences have resulted from the close collaboration. The role of foreign collaborators will be expressed by participating in the discussion of research findings during the work on the Project, providing comments on the quarterly, annual and final reports and joint publications.
Technical Approach and Methodology. The Project will use present-day and classical methods for cultivation and classification of soil microorganisms, chemical, biochemical, physic-chemical and biotechnological techniques, procedures for cleaning and studying the chemical nature of biologically active substances, as well as the methodology of their biotesting. Studies on the taxonomy of extremophilic actinomycetes, biosynthesis of antibiotics produced by them, obtaining pure substances of antibiotics and determining their chemical nature will be carried out at the Institute of Microbiology and Virology, CS MES RK (Lead organization in the Project). Studying antimicrobial properties of the new antibiotics against agents of life-threatening infections will be carried out at the M. Aykimbaev Kazakh Scientific Center for Quarantine and Zoonotic Diseases, MNE RK (another participating Institute 1).
