Bacteria.no

How phages affect the body

Rostec Blog, Naked Science

Bacteriophages are viruses that infect and destroy only bacteria. Back in the last century, pharmacists learned to use the properties of these tiny assistants to fight diseases for the benefit by creating therapeutic and prophylactic antibacterial drugs based on them. They have been successfully used to treat infectious diseases for almost a hundred years and they are safe even for newborns. But medicine continues to investigate the features of bacteriophages, and this work is far from finished. In the last article, which opened a series of articles about phages, we wrote about the contribution they made to science. Today, the expert of the holding "Natsibio" of the Rostec State Corporation, the head of the project office for the study of bacteriophages, Alexander Zharnikov, talks about some scientific hypotheses concerning the effect of these viruses on the human body.

Photo of a bacteriophage taken with an electron microscope / ©The press service of "Natsibio"

The first article of the cycle about bacteriophages can be found here. I must say that our interest in these tiny but useful viruses is not accidental – recently, not only representatives of the Russian, but also the global medical community have been showing increasing interest in them.

After all, drugs based on them can become an alternative to antibiotics in the treatment of infections. This is because bacteriophages are able to multiply only in the presence of a certain type of pathogenic bacteria, without destroying useful microorganisms, which helps to cope with the disease, preserving the natural microflora of the body.

In our world, bacteriophages are present everywhere — in the ocean, soil, deep-sea springs, drinking water, food and, of course, in the human body. And despite the fact that medicine has accumulated a large evidence base on the effectiveness and safety of the use of bacteriophages as antibacterial agents, scientists still wonder: can these viruses directly affect the human body?

Today, such fundamental research has already begun in different countries of the world. Their first results turned out to be very interesting: in particular, bacteriophages may be able to have immunomodulatory and anti-inflammatory effects on the body. But at this stage of the development of these studies, it is necessary to recognize that it is too early to draw conclusions about the possibility of using these effects in medicine.

"Viruses for immunity"

There is a large viral community in our body – virom. And various bacteriophages are widely represented in it – bacterial viruses, which, in turn, form a phage. Phagoma bacteriophages can freely penetrate through the mucous membranes into the blood, and in various ways, and reach the lymph nodes. For example, phages enter the bloodstream through a damaged mucous membrane or use bacteria as a "transport".

Scientists estimate that about 30 billion phages migrate from the intestine to the tissues every day. And even in the most protected environment of our body – the cerebrospinal fluid – these viruses are also present. What do they do in the blood and nervous system? Scientists cautiously suggest that bacteriophages help fight dangerous microorganisms, affect the work of the immune system and metabolism.

What is the basis of this assumption? The fact is that the human immune system consists of many links intertwined by complex interactions. It has been found that bacteriophages can influence various mechanisms of immune defense. One of them is phagocytosis. There is a special group of "devouring cells" - phagocytes. They are able to absorb foreign particles, and then destroy them or expose antigens on their surface and go to the lymph nodes to "introduce" lymphocytes to them.

There is evidence that phages enhance bacterial phagocytosis. Firstly, phage particles literally cling to the bacterial cell from all sides and help phagocytes recognize it. Secondly, a phagocyte can swallow a bacterium that is already infected with a phage. The virus continues to destroy the victim from the inside and accelerates its "digestion".

These considerations are partly confirmed in practice. For example, in 2007, the results of a study were published, during which a bacteriophage drug was injected into the sinuses of patients with chronic purulent inflammation in the nasal cavity and paranasal sinuses. It turned out that this helped phagocytes to devour bacteria more successfully and bring this process to an end.

In addition, the phages activated neutrophils – one of the varieties of leukocytes. It is known that these viruses help prevent the recurrence of diseases of the ENT organs and prevent their transition to a chronic form. Despite some positive conclusions about the effect of phages on immunity, this issue requires further study.

Fighters with inflammation

Inflammation is a protective function of the body, and it is provided by innate immunity. But sometimes the inflammatory process is so strong and prolonged that it does more harm. And with this problem, as some studies show, bacteriophages can help.

On the one hand, anyway, bacteriophages are "strangers" to the human body. Although they do not attack our cells, but the defense mechanisms respond to them. However, studies show that if phages have the ability to provoke an inflammatory response of the body, it is almost invisible.

But the anti-inflammatory effect can be very pronounced. In particular, it is suggested that phages may have a protective potential, not only destroying pathogens, but also suppressing local immune and inflammatory reactions in the intestine, thereby contributing to the maintenance of immune homeostasis (maintaining the immune system in optimal physiological conditions). This helps to avoid unnecessary tissue damage and accelerate the fight against infection.

Due to the specific and rather complex mechanism of action, bacteriophages, of course, cannot be considered as a substitute for more effective aspirin or ibuprofen tablets. But it is useful to know about their anti-inflammatory potential.

Viruses against Viruses

In recent years (and especially against the background of the Covid-19 pandemic), scientists have been increasingly talking about the potential antiviral effects of bacteriophages. In fact, this question has been investigated for more than half a century. Phages interfere with the course of viral infection through various mechanisms. They stimulate the production of interferon, occupy receptors on cells, preventing viruses from joining them, and are able to cause cross-immunity: after "getting acquainted" with the phage, the immune system more easily recognizes viruses with similar antigenic properties. Penetrating into epithelial and some other cells, bacteriophages protect them from death caused by viral infection.

It is also important to remember about such a phenomenon as a secondary bacterial infection. For example, deaths from Covid-19 often occurred from bacterial pneumonia that joined the infection. To counteract such a tragic development of the disease, the American FDA agency approved the use of phage therapy.

It is quite possible that the beneficial properties of bacteriophages are not limited to those listed in this article. Phage therapy has great prospects, and in order to fully reveal it, the work of virologists, biologists, geneticists, doctors, and other specialists is required.

By the way, the world's only manufacturer of medicines based on bacteriophages on an industrial scale, the company NPO Microgen (part of the holding company Natsibio of Rostec State Corporation) is located in Russia. The scientists of the enterprise are actively engaged in studying the beneficial properties of bacteriophages on the basis of their own Biological Resource Center, where an in-depth study of bacteriophages is conducted using current scientific technologies and modern equipment.

The Biological Resource Center combines a phage bank (a collection of characterized bacteriophages with a decoded genome), a molecular genetic laboratory and a selection unit into a single functioning structure. Today, scientists can photograph bacteriophages, study their biological properties and decipher genetic material, which allows faster and more complete investigation of the nature of bacterial viruses and its effect on the human body.

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