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“One Health-One Medicine” approach by use of bacteriophages

#G-2405


Development of the universal phage-based preparation against human and animal pathogens: Salmonella spp, E.coli, and Enterococcus spp.

Tech Area / Field

  • AGR-DIS/Disease Surveillance/Agriculture
  • AGR-VTH/Vaccines and Theraupetics/Agriculture
  • BIO-IND/Industrial Biotechnology/Biotechnology
  • BIO-SFS/Biosafety and BioSecurity/Biotechnology
  • MED-DIS/Disease Surveillance/Medicine
  • MED-DRG/Drug Discovery/Medicine

Status
3 Approved without Funding

Registration date
05.09.2017

Leading Institute
Eliava Institute of Bacteriophage, Microbiology&Virology, Georgia, Tbilisi

Supporting institutes

  • Institute of Molecular Biology, Armenia, Yerevan\nInnovative University of Eurasia, Kazakhstan, Pavlodar reg., Pavlodar

Collaborators

  • Cork Institute of Technology, Ireland, Cork\nPANTEX Hlland BV, The Netherlands, Hapert\nUniversity of Ghent, Belgium, Ghent\nUniversity College London, UK, London\nQueen Astrid Military Hospital, Belgium, Brussels

Project summary

The Project aim is - To search for the efficient strategy for use of and bacteriophages for prevention of the food-borne diseases disseminated through the food chain from animals to humans. In this regards, the target pathogens are: Salmonella spp., E. coli, and Enterococcus spp typically causing swine and chicken infections. The goal of the project will be achieved by taking into account a concept of “one medicine”, which is accepted by the American Medical Association and the American Veterinary Medical Association, as a basic idea.
Current status. The One Health concept recognizes that the health of people is connected to the health of animals and the environment. CDC uses a One Health approach by working with physicians, veterinarians, ecologists, and many others to monitor and control public health threats and to learn about how diseases spread among people, animals, and the environment. A One Health approach is important because 6 out of every 10 infectious diseases in humans are spread from animals. There are many examples that show how the health of people is related to the health of animals and the environment. For instance, some diseases can be shared between animals and people. These diseases are known as zoonotic diseases (e.g. anthrax, brucellosis, salmonellosis, escherichiosis, etc.) [1]
About two-thirds (60.3 %) of emerging infectious diseases (EID) result from zoonoses; the majority of these have their origin in wildlife (71.8%) and have been increasing in recent years. The researchers found that over 50% of EID events were due to bacteria, and that their database included a large number of drug resistant organisms [2].
The bacteria Salmonella spp., E. coli, and Enterococcus spp., which are commonly isolated from pigs and chicken at slaughter and contaminated products, are considered to be a source of human infections all over the world including various ex-soviet countries as well. These pathogens may present a serious threat to human health as they carry multi drug resistant genes which makes them sometimes untreatable.
The threats posed by EIDs are dynamic. EIDs are caused by pathogens that can change their behavior over time – either through genetic modification or through changes in the patterns and pathways of transmission [3]. Although principally associated with EID prevention and control, One Health is also relevant to prevention and control of endemic and zoonotic animal diseases, as well as securing food safety [4, 5]. Most of EID diseases are spread from animals to humans through the food chain and are known as food-borne infections. The majority of the emerging infectious diseases, including those caused by bioterrorist agents, are zoonoses. These infections if used for bioterrorist purposes may cause much more extended damages than e.g. anthrax [6].
Therefore, seeking for management strategies that can prevent or reduce food-borne infections is extremely important.
In the 20th century, Calvin Schwabe coined the concept of “one medicine”. It recognizes that there is no difference of paradigm between human and veterinary medicine and both disciplines can contribute to the development of each other [7]. Bacteriophages (phages) may perfectly fit into the “one medicine” concept as they are the most abundant organisms in the biosphere. The estimated number of bacteriophages on earth attains 10 31. Presently bacteriophages (bacterial viruses) are considered as alternatives to antibiotics and disinfectants.
The idea of use of bacteriophages for treatment of animal and human diseases was first suggested by French-Canadian scientists Felix d’Herelle in 1917. A centennial anniversary of this discovery has been widely celebrated this year at the Pasteur Institute (Paris, France) and Eliava Bacteriophage Institute (Tbilisi, Georgia) - the cradle of bacteriophage research set by Felix d’Herelle. After the discovery of bacteriophages the concept of phage therapy became very popular worldwide, however the advance of antibiotic era switched the interest of researchers to these antibacterial agents. For a long time bacteriophage therapy remained popular only in Georgia, Russia, and in the EU member country, Poland. However, in the western medicine, there also has been a recent resurgence of interest in phage therapy due to the emerging problem of antibiotic resistance among bacterial pathogens. As bacteriophages are having absolutely different mode of action against bacteria, they are showing high effectiveness to multi-drug-resistant pathogens. Phages display a number of unique features compared to antibiotics. First of all, they are much more specific than antibiotics and could target a specific problematic bacterium, without affecting the normal commensal microbiota, which plays an important role in human health and well-being. Because of their high specificity to target bacteria bacteriophages are not harmful to plants, animals and humans, at the same time they are efficiently killing drug-resistant bacteria.
The project’ influence on progress in this area Although there is a vast experience of use bacteriophages for therapy and prophylaxis of bacterial diseases in humans, the effect of this approach was much less studied in veterinary. Designing of bacteriophage preparations challenging animal and human common pathogens will lead to development of the universal phage preparation for control of food-borne infections.
The participants’ expertise: The scientists taking part in the project have considerable experience in bacteriophage research, phage therapy and prophylaxis as well as in uncovering molecular mechanism of phage-bacteria interactions, which is reflected in their publications and participation in the international conferences. This information is available on the Internet web-site http://www.eliava-institute.org. The present proposal is a continuation of the previous project (A-2140), which has been was implemented together with IMB (Armenia). Within the frames of A2140 project, a large collection of Salmonella isolates obtained from salmonellosis patients, food, and environmental sources has been created and well-characterized. The Salmonella strains from our collection were tested for susceptibility to 20 phage clones. The phages showing 90-99% of coverage were selected for designing a prototype of the anti-salmonella commercial phage preparation. These phages were tested also against the Salmonella strains of veterinary origin (EU-7FP-2011-IAPP-606464). A number of these phages showed >90% coverage of the veterinary strains as well. These results indicate that the phages are having a broad spectrum of action and may be equally effective towards human and animal pathogens. Besides that the Leading institution has studied disinfecting potential of bacteriophages (INTAS -6610) in a laboratory model experiment. [53].. However, large scale (field, farm) experiments have never been performed as yet because of lack of funding.
All above described achievements are the prerequisites for successful implementation of the tasks set in this project which will lead to commercialization of the developed phage-based product challenging “One Health-One Medicine” strategy.

Scope of activities. The following activities will be implemented under the Project:
    - Continuation and strengthening the previously established collaborative network of researchers in Armenia, Georgia, Kazakhstan and collaborating countries for the development of efficient alternatives to antibiotics in the form of phage therapy.
    - Isolation of Salmonella, E.coli and Enterococcus strains of animal origin and comparison to human isolates to identify the animal reservoirs of these zoonotic infections.
    - Isolation and characterization of lytic phages to identify the most efficient clones.
    - Development of a prototype of the complex bacteriophages preparation active against Salmonella spp., E.coli and Enterococcus spp. of human and animal origin
    - Demonstration of the prophylactic effect of the complex bacteriophages preparation in the farm experiments on 0-21 day piglets and chicks.
    - Demonstration of the disinfecting effect of the complex bacteriopphage preparation in the farm experiment through prophylactic sanitation of stalls, cages, slaughter facilities, etc.
    - Commercialization of the complex “One Health-One Medicine” phage preparation elaborated during the project.
    - Presentation of the results to the international scientific community.


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