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Bacteriophage as an Alternative to Antibiotics

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Bacteriophage Against a Number of Medication Resistant Conditionally – Pathogenic Bacteria – as an Alternative to Antibiotics

Tech Area / Field

  • BIO-MIB/Microbiology/Biotechnology
  • MED-OTH/Other/Medicine

Status
8 Project completed

Registration date
21.06.2000

Completion date
19.01.2007

Senior Project Manager
Rudneva V Ya

Leading Institute
Biochimfarm Joint Stock Company, Georgia, Tbilisi

Collaborators

  • The Evergreen State College, USA, MD, Washington\nHumboldt Universität / Humboldt University School of Medicine Charite, the Institute of Virology, Germany, Berlin

Project summary

The aim of the presented work is to select and research specific phages for the therapy of infections caused by antibiotic - resistant opportunistic pathogens: Pseudomonas aeruginosa, Serratia marcescens and Enterococcus.

All mentioned microorganisms are characterized by high natural and acquired resistance even to super-new anti-microbe substances. Their role becomes more substantial during the origin of infections at hospitals – at children hospitals, surgery hospitals, burn trauma centers, urology departments, etc. The most acute processes are observed on the background of immune-depression with newborn children, difficult surgery, immune system diseases, etc.

The creation of new effective and safe preparations such as bacteriophages, acquires more and more relevance for the practical medicine. The prospects of their utilization are determined by their high specificity, target effect of the chosen bacteriophage, absence of correlation between the action of a bacteriophage and the resistance of bacteria towards other medical preparations.

The project implementation suggests the selection and study of bacteriophages by lytic spectrum, scope of activity and virulence that will enable the purposeful construction and elaboration of methods for the production of highly purified various medicational bacteriophages: Pseudomonas aeruginosa, Serratia marcescens and Enterococcus.

The great experience in the production and usage of phage preparations for medication –preventive purposes have been accumulated in the ex-Soviet Union in decades. The Tbilisi Institute of Bacteriophages, Microbiology and Virology the production of medicational – preventive bacteriophage preparations are carried out since the establishment of the Institute and are still underway.

The authors of the proposed project were the first in the ex-Soviet Union who produced and registered and launched the production of the medicational bacteriophage Pseudmonas aeruginosa back in the 70-ies and selected the anti-microbe medicational phage Serratia marcescens. The project is carried out by the joint stock company “Biochimpharm” that was established on the base of the ex Department for the Production of Bacteriophages under the Tbilisi G. Eliava Institute of Bacteriophages, Microbiology and Virology that have been producing commercial bacteriophagic preparations against intestinal infections for the needs of the ex Soviet Union in great quantities since the forties.

The personnel, engaged in the project, have theoretical background and practical skills in the sphere of microbiology, bacteriophage, immunology and medicine. They have published scientific works.

The proposed project can be ascribed to the category of fundamental and applied researches as well as the elaboration and demonstration of technologies. The final results of the conducted works might be as follows:

1. Selection of new medicational phages; research of their host environment, activity and stability of lysis.

2. Study of basic taxonomic traits of separate phage clones within the framework of the demands of the International Committee for the Calssificatio of Viruses: virion morphology, molecular structure of nucleocapsides, molecular structure of genome..

3. Enhancing the knowledge on genuine virulent character of phages: the nature of nitrogen base distribution on DNA – the the ability to reproduce on the UV inactivated bacterial cells and the determination f the phenomenon of non-clasic modification – restrictionas an additional criterium for the virulence of medicational bacteriophages.

4. Elaboration of methods for the production of highly effective purified medicational bacteriophage preparations, specific against the opportunistic highly antibiotic-resistant microbes.

5. Construction of experimental – laboratory series of medicational preventive preparations of bacteriophages against Serratia marcescens Pseudonomas aeruginosa and Enterococus, in vitro and in vivo inspection of theie efficiency.

6. Elaboration of recommendations for the production of highly active, purified medicational bacteriophage preparations.

The utilization of bacteriophages will promote the decrease in the overall morbidity rate, lessen the post-surgery complications and other inter-hospital infections risen by microorganisms: (Serratia marcescens, Pseudomonas aeruginosa and Enterococcus) that will result in definite social – economic effect.

The collaborators agree to cooperate in scientific – research activities envisaged by the project, exchange information in the process of its implementation, discuss report materials and in case of necessity provide consultations, discuss the results at conferences, visit the participants of the project and invite them as well.

The following methods of research will be used in the realization of the project: determination of morpho-cultural traits of bacterial strains; selection of virulent phages and determination of their morphology with the aid of electronic microscopy, reception and purification of bacteriophages by the method of ultrafiltration, ultracentrifugation in different gradients, etc.; study the phage propagation cycle; influence of physical – chemical factors on the vitality of phages, reception of anti-phage serum on rabbits, research of serologic characteristics of phages under the neutralization method; determination of the scope, specific effect of phages on homo and heterological strains, cross phago-resistance and stability of a lysis.


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