Viruses against bacteria, renewed hope for treating antibiotic-resistant infections: bacteriophage therapy. Let’s see what bacteriophage therapy research has achieved in this field.

Antibiotics have been one of the major medical advances of the twentieth century to reduce major infectious diseases: tuberculosis, leprosy, pests, many sexually transmitted infections … However, their massive and sometimes excessive use in humans and animals, combined with the slowdown in the discovery of new classes of antibiotics, is leading today to the development of more and more bacteria resistant to existing treatments.

Antibiotics have reached their limit. Bacteria have become increasingly adapted and require more and more heavy and toxic treatments that sometimes combine several antibiotics. Another phenomenon that is growing: the infections associated with care, which are acquired during hospitalization – nosocomial diseases -. A growing share of hospital-acquired infections is due to multi-drug resistant bacteria.Bacteriophage Therapy Research

*** White Blood Cell Surrounded by Bacteria

Antibiotic resistance – the increasing resistance of microbes to antibiotics – is a major problem at the national and international levels. The massive use of antibiotics in humans and animals has led to the selection of multi-resistant bacteria. In addition, WHO has seen a significant increase in antibiotic resistance over the last 30 years and warned that if nothing was done to prevent the misuse of antibiotics or to find new molecules, the world would move towards a post-antibiotic era, in which common infections can start killing again.

Bacteriophage Therapy Research Could Become an Attractive Alternative

Antibiotic research is at a standstill against these resistances (which also evolve very rapidly), the bacteriophage therapy research could become an attractive alternative.

Over the past fifteen years, this old therapy has been the subject of renewed interest in countries such as the United States, Belgium, and France, alongside the development of antibiotic resistance, a challenge for women. the scale of the planet. Today, antibiotic resistance and the lack of development of new antibiotics have put bacteriophage therapy on the front of the stage.

What is the history of bacteriophage therapy research? What is bacteriophage therapy? What are the advantages and limitations of bacteriophage therapy? How are phages applied in the agri-food industry?

I – Bacteriophage Therapy Research Through History

Bacteriophage Therapy Research Before the Second World War

Discovered in 1915 by Frederick W. Twort in London, then observed again in 1917 by Félix d’Hérelle, and isolated by the latter, these bacterial-eating viruses knew from that time their first applications in the treatment of large infections and revealed publicly their early successes in the early 1920s.

George Eliava, who had worked at the Institut Pasteur in Paris with d’Hérelle, founded a virology Institute in Tbilisi, Georgia, in 1923. Together, in adapted premises, they developed from 1930 the study of bacteriophages and the application of bacteriophage therapy for the whole of the Soviet Union.

The George Eliava Institute has a large collection of therapeutic bacteriophages. Georgian phage therapists have eighty years of clinical experience in this field.

In Poland, an Institute of Immunology and Experimental Therapy has also continued to use phage therapy.

In the rest of the world, before the Second World War, the marketing of phage products was undertaken by major pharmaceutical companies like Eli Lilly in the United States, Robert & Carrière (absorbed today by Sanofi-Aventis) in France.

Scientists Stopped Using and Studying Phage Therapy Because of Antibiotics

When antibiotics were discovered in 1941, they were widely marketed in the United States and Europe, so most western scientists stopped using and studying phage therapy.

The Cold War has banned eastern European countries from access to antibiotics produced by the Western pharmaceutical industry. Cut off from Western progress in antibiotic production, scientists in the Soviet world have continued to perfect their treatments. For example, one of the largest phage banks is in Tbilisi, Georgia. Today, the Institute remains functional only thanks to the support of Western structures and the Georgian State.

Bacteriophages Against Cholera

The Defense Threat Reduction Agency, founded with the aim of “protecting the United States and its interests from weapons of mass destruction”, has invested in the renovation of the Eliava main building and laboratories and is funding a number of scientific projects, including bacteriophages against cholera.

Phage Therapy Center

Tbilisi, Georgia is home to the Phage Therapy Center, which also offers a treatment program for infections refractory to conventional therapies. The testimonies of unexpected healings are as numerous as they are astonishing. And studies of patients whose condition was dramatic reports that these people, sentenced to certain death, have been treated with phages, and all were saved by them.

In Russia

In Russia, this technique has been preserved, so that phages are used in space to heal astronauts. Indeed, when we turn our eyes to the countries of the East, we discover an incredible breakthrough in the treatment of the most serious infections, as well as real scientific research dedicated to this neglected method.

 

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II – What is Bacteriophage Therapy?

Bacteriophage therapy – discovered during the First World War and developed in the 1920s and 1930s – is based on the use of bacteria-eating viruses (or phages) to treat certain infectious diseases of bacterial origin.

“Phage” corresponding to the Greek root of “food”, literally a bacteriophage is an “entity”, actually a virus, which eats bacteria.

A Huge Diversity of Phages

There is a huge diversity of phages that are ubiquitous in our environment (in seawater, lakes, sewers), including in our digestive system. A peculiarity of phages is to be each very specific to a specific type of bacterium, which has a double advantage: to attack only the pathogenic bacteria without killing the “good bacteria” – unlike antibiotics that have a broad spectrum-, and especially not to infect human cells. The phage virus enters the bacterium, it multiplies and destroys it. Phage is eliminated when the pathogenic bacterium is eradicated.

The Most Important Biomass on the Planet

Bacteriophages are the most important biomass on the planet. Considering that there would be ten to a hundred times more than bacteria, there is an average of 107 phages per ml in liquid media and up to 109 in sediments.

In a human body, in particular, we have on average 5 kg of worker bacteria without which we could not survive. In the first line is the intestinal flora which is the main guardian of our health.

III – Advantages of Bacteriophage Therapy

Bacteriophage therapy is generally considered safe. It has a rapid action, almost immediate, as soon as the exact bacterium is identified and the phages are administered. Bacteriophages are often very specific, addressing only one or a few strains of specific bacteria. Phages are chosen so as not to harm useful bacteria such as those normally present in the intestinal flora, on the mucous membranes or on the skin. This reduces the likelihood of opportunistic infections that develop after the selection of certain minority bacteria during antibiotic therapy.

Bacteriophage Therapy Could Be Used in Many Infections

Bacteriophage therapy could be used in infections that affect the bones and joints, but also in other infections, urinary, pulmonary, ocular.

The key advantage of bacteriophage therapy is that it works on antibiotic-resistant bacterial strains without making them more and more recalcitrant over time, as the phage responds to a natural process that balances bacteria.

Bacteriophage Target Precisely One Bacteria

Unlike antibiotics which, because of their too general spectrum, usually have a more general effect, destroying both harmful bacteria and intestinal flora (our internal bacteria), phages have the advantage of targeting precisely one bacteria while evolving, adapting in a coordinated way with the latter, thus facing its possible resistance.

IV – Limitations of Bacteriophage Therapy

Their application in humans seems limited to infections where the bacteriophage can be brought into contact with the bacteria. All that requires the injection of phages – septicemia, parenchymal infections – seems doomed to failure since the phages will in principle be destroyed by the immune system.

Bacteriophages do not enter cells other than bacteria. They are unsuitable for treating infections caused by intracellularly propagated bacteria.

Bacteria Can Acquire Resistance to Bacteriophages

Effective administration of bacteriophages requires an accurate diagnosis of the infection. Not only is it essential to know which species of bacteria cause the infection, but also which strain of it. As with antibiotics, bacteria can acquire resistance to bacteriophages used in treatments.

Another limit to the use of bacteria-killing viruses: the protection of the biological balance of the environment.

Bacteriophages Are Not Patentable

Insofar as the products intended for the bacteriophage therapy contain only natural phages, these will be impossible to protect by a patent, since they come from nature.

Pharmaceutical companies are not interested in this project because bacteriophages are not patentable, and therefore not profitable. Pherecydes-Pharma is the only private laboratory to test phage drugs that can treat staphylococcus aureus and certain respiratory infections.

V – Bacteriophage Therapy Research in the Agri-Food Industry

Foodborne diseases (ETA) are those of an infectious or toxic nature, caused mainly by the consumption of contaminated foods or beverages. The World Health Organization estimates that 2 million people die from diarrheal diseases each year.

Food and water safety is a global issue and it is easy to see the devastating effects of food contamination in market news from almost every region. It is at stake in the world market because hundreds of millions of dollars in food products are removed and discarded because of pollution, human infection, disease, and death.

The Risk of Acquiring a Foodborne Illness

The risk of acquiring a foodborne illness (ETA) occurs when food is altered and contaminated with pathogenic bacteria; such an event takes place by cross-contamination through the raw material, process or worker.

In the agri-food industry, phage-prophylaxis has been considered to eliminate potentially pathogenic bacteria in the food chain from farms to the processing industry.

Listeria Species in the Dairy Industry.

In the United States, it is used to destroy certain bacteria that can contaminate fresh food products such as meat, poultry, and fish. For several years, the FDA has authorized the marketing of a commercial preparation intended to eradicate the Listeria species in the dairy industry. It has also been imagined agri-food use on a larger scale and especially in aquaculture to reduce the intensive use of antibiotics.

The Listx, for example, a Dutch preparation of phages that attack the bacteria responsible for listeriosis, has been approved in the United States, Canada, and is potentially usable in Europe.

Polymers of microbial origin are uniform and pure products. In the case of bacterial cellulose, produced for example by Acetobacter xylinum, these characteristics make it possible to produce acoustic membranes of great firmness and thus to successfully compete with vegetable cellulose.

A Product Called Agriphage

A product called Agriphage is currently being applied to a wide range of cultures to combat specific bacteria with remarkable success; the treatment of plants from the seed phase to its development, results in a wide variety of crops including agribusiness ranging from tomatoes, peppers, lettuce, cabbage, and melons, to crops such as strawberries, apples, pears, and even citrus and ornamental plants. This technology makes it possible to treat virtually every type of crop in every geographic region and in diverse climates.

Biopreservation

Biopreservation is a conservation method that aims to extend the shelf life of food and improve safety. Lactic acid bacteria, because of their technological, nutritional and possibly therapeutic characteristics, play a central role in the treatment of milk to obtain fermented products such as cheeses and yogurts. By fermentation, lactic acid bacteria confer the particular organoleptic and rheological properties of fermented milk products.

In biotechnology, bacteriophages can be used as indicators of faecal pollution in water and soil as well as in phage typing and bacterial identification. They are recently used as a biological control in foods, applying to a variety of fresh products, fruits, juices, meat. They are also used in the treatment of wastewater (bio-remediation).

As a Conclusion

There is a benefit to using antibiotics and bacteriophages not only for their synergistic effects but also because both antibiotics and bacteriophages are irreplaceable in certain situations. Antibiotics and bacteriophages are not competitors but complementary and bacteriophage therapy should be considered as an additional weapon in the arsenal of the fight against bacterial infections.

It is becoming urgent today to move towards other therapeutic means. For this, phage therapy represents a solid hope in the treatment of the most difficult infections to fight. No doubt, it is possible to envisage coupled treatments comprising antibiotics with global action and phages with targeted action.

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