Big war with a small enemy, or how to destroy bacteria. A big war with a small enemy, or how to destroy bacteria The process of destroying microbes by eating cells

Option 1

A1. What is the name of the science of the structure of man and his organs?

1) anatomy 3) biology

2) physiology 4) hygiene

A2. What part of the brain is called the small brain?

1) midbrain 3) medulla oblongata

2) spinal cord 4) cerebellum

A3. What muscle group do the temporalis muscles belong to?

1) to mimic 3) to respiratory

2) to chewing 4) to motor

A4. What is the name of the process of destruction of microbes by consuming cells?

1) immunity 3) phagocytosis

2) brucellosis 4) immunodeficiency

A5. What is the name of the enzyme of gastric juice that can only act in an acidic environment and breaks down protein into simpler compounds?

1) hemoglobin 3) cerebellum

2) pituitary gland 4) pepsin

A6. What is the name of the nerve structures that convert perceived stimuli into nerve impulses?

1) sensitive neurons 3) intercalary neurons

2) receptors 4) synapses

A7. What is an excessive increase in blood pressure called?

1) hypertension 3) hypotension

2) allergy 4) arrhythmia

IN 1. What are the functions of the nervous and endocrine systems?

IN 2. What is the name of the constant composition of the fluids that make up the internal

Wednesday?

AT 3. What is the name of a liquid containing weakened microbes or their poisons?

AT 4. Who discovered central braking?

AT 5. What are the rhythmic vibrations of the walls of arteries called?

C1. What secretion gland does the pancreas belong to? Explain why?

C2. What are the consequences of kidney failure in humans?

Biology test for the 8th grade course

Option 2

A1. What is the name of the warm salty liquid that connects all human organs with each other, providing them with oxygen and nutrition?

1) tissue fluid 3) lymph

2) blood 4) intercellular fluid

A2. What is the name of the part of the brain that provides coordination and coordination of movements, as well as the balance of the body?

1) medulla oblongata 3) cerebellum

2) hypothalamus 4) midbrain

A3. What type of tissue is bone tissue?

1) connective 3) muscular

2) epithelial 4) nervous

A4. What makes up the bulk of plasma?

1) lymph 3) erythrocytes

2) water 4) shaped elements

A5. What is the name of the largest gland in our body, located in the abdominal cavity under the diaphragm?

1) thyroid 3) pancreas

2) spleen 4) liver

A6. What is the contact between neurons and cells of the working organs?

1) with the help of synapses 3) with the help of the vagus nerve

2) with the help of alveoli 4) with the help of receptors

A7. What is lymph formed from?

1) from blood 3) from tissue fluid

2) from intercellular substance 4) from gastric juice

IN 1. What is the name of the transparent semi-liquid mass that fills the interior of the eyeball?

IN 2. What does it consist of Gray matter brain?

AT 3. What is the name of the lack of vitamins in the body?

AT 4. Where does gas exchange take place?

AT 5. What is the name of the ability of an organ to be rhythmically excited under the influence of impulses arising in it without external stimuli?

C1. Name at least 3 criteria that allow us to classify humans as mammals.

C2. Is it possible for a person with blood type II to transfuse blood type III and why? Why can blood of group I be transfused to all four groups?

Answers

Option 1

A1 - 1

A2 - 4

A3 - 2
A4 - 3

A5 - 4
A6 - 2

A7 - 1

B1 - regulatory
B2 - homeostasis

B3 - vaccine

B4 - I.M. Sechenov

B5 - pulse

C1 - Mixed secretion. Part of the cells of the pancreas secretes hormones (insulin) directly into the blood, the other part - pancreatic juice, which enters the duodenum through the ducts.

C2 - Kidneys - an organ of the excretory system. Violation of their work can lead to disruption of homeostasis (changes in the composition of the internal environment) and poisoning of the body with metabolic products.

Option 2

A1 - 2

A2 - 3

A3 - 1
A4 - 2

A5 - 4
A6 - 1

A7 - 2

B1 - vitreous body
B2 - from the bodies of neurons

B3 - hypovitaminosis

B4 - in the alveoli of the lungs and tissues

B5 - automatism

C1 - the presence of the uterus and mammary glands, the lungs are of the alveolar type, the heart includes 4 chambers, constant temperature body, thoracic and abdominal cavities are separated by a diaphragm.

C2 - it is impossible, because the meeting of agglutinins β contained in the blood of group II with agglutinogens B contained in the blood of group III will lead to agglutination. There are no agglutinogens A and B in the blood of the group, so it can be transfused to all blood groups.

Criteria for evaluating responses

For each correctly completed task under the letter A, 1 point is awarded, a total of 7 points.

For each correctly completed task under the letter B, 2 points are awarded, a total of 10 points.

For each correctly completed task under the letter C, 3 points are awarded, a total of 6 points.

Total - 23 points

80-100% - rating "5"

60-80% - grade "4"

40-60% - grade "3"

0-40% - score "2".

Explanatory note

For intermediate certification in biology in the 8th grade a set was compiled test items(2 options). They are compiled taking into account the state educational standard. Content educational material correlated with the amount of time devoted to the study of biology in the 8th grade by the basic curriculum(2 hours per week / 68 hours per year).

All questions and tasks are divided into three levels of difficulty (A, B, C).

Level A - basic (A1-A7). Each question has 4 possible answers, only one of which is correct.

Level B - contains 5 tasks (B1-B5). Each task of this level requires a short answer (in the form of one or two words).

Level C - increased complexity contains 2 tasks (C1-C2). This assignment requires you to write a detailed answer.

For execution control work 45 minutes are allotted (1 lesson).


Option 1

A1. What is the name of the science of the structure of man and his organs?

1) anatomy 3) biology

2) physiology 4) hygiene

A2. What part of the brain is called the small brain?

1) midbrain 3) medulla oblongata

2) spinal cord 4) cerebellum

A3. What muscle group do the temporalis muscles belong to?

1) to mimic 3) to respiratory

2) to chewing 4) to motor

A4. What is the name of the process of destruction of microbes by consuming cells?

1) immunity 3) phagocytosis

2) brucellosis 4) immunodeficiency

A5. What is the name of the enzyme of gastric juice that can only act in an acidic environment and breaks down protein into simpler compounds?

1) hemoglobin 3) cerebellum

2) pituitary gland 4) pepsin

A6. What is the name of the nerve structures that convert perceived stimuli into nerve impulses?

1) sensitive neurons 3) intercalary neurons

2) receptors 4) synapses

A7. What is an excessive increase in blood pressure called?

1) hypertension 3) hypotension

2) allergy 4) arrhythmia

IN 1. What are the functions of the nervous and endocrine systems?

IN 2. What is the name of the constant composition of the fluids that make up the internal

AT 3. What is the name of a liquid containing weakened microbes or their poisons?

AT 4. Who discovered central braking?

AT 5. What are the rhythmic vibrations of the walls of arteries called?

C1. What secretion gland does the pancreas belong to? Explain why?

C2. What are the consequences of kidney failure in humans?

Biology test for the 8th grade course

Option 2

A1. What is the name of the warm salty liquid that connects all human organs with each other, providing them with oxygen and nutrition?

1) tissue fluid 3) lymph

2) blood 4) intercellular fluid

A2. What is the name of the part of the brain that provides coordination and coordination of movements, as well as the balance of the body?

1) medulla oblongata 3) cerebellum

2) hypothalamus 4) midbrain

A3. What type of tissue is bone tissue?

1) connective 3) muscular

2) epithelial 4) nervous

A4. What makes up the bulk of plasma?

1) lymph 3) erythrocytes

2) water 4) shaped elements

A5. What is the name of the largest gland in our body, located in the abdominal cavity under the diaphragm?

1) thyroid 3) pancreas

2) spleen 4) liver

A6. What is the contact between neurons and cells of the working organs?

1) with the help of synapses 3) with the help of the vagus nerve

2) with the help of alveoli 4) with the help of receptors

A7. What is lymph formed from?

1) from blood 3) from tissue fluid

2) from intercellular substance 4) from gastric juice

IN 1. What is the name of the transparent semi-liquid mass that fills the interior of the eyeball?

IN 2. What is the gray matter of the brain made of?

AT 3. What is the name of the lack of vitamins in the body?

AT 4. Where does gas exchange take place?

AT 5. What is the name of the ability of an organ to be rhythmically excited under the influence of impulses arising in it without external stimuli?

C1. Name at least 3 criteria that allow us to classify humans as mammals.

C2. Is it possible for a person with blood type II to transfuse blood type III and why? Why can blood of group I be transfused to all four groups?

Answers

Option 1

A3 - 2
A4 - 3

A5 - 4
A6 - 2

B1 - regulatory
B2 - homeostasis

B3 - vaccine

B4 - I.M. Sechenov

B5 - pulse

C1 - Mixed secretion. Part of the cells of the pancreas secretes hormones (insulin) directly into the blood, the other part - pancreatic juice, which enters the duodenum through the ducts.

C2 - Kidneys - an organ of the excretory system. Violation of their work can lead to disruption of homeostasis (changes in the composition of the internal environment) and poisoning of the body with metabolic products.

Option 2

A3 - 1
A4 - 2

A5 - 4
A6 - 1

B1 - vitreous body
B2 - from the bodies of neurons

B3 - hypovitaminosis

B4 - in the alveoli of the lungs and tissues

B5 - automatism

C1 - the presence of the uterus and mammary glands, the lungs are of the alveolar type, the heart includes 4 chambers, a constant body temperature, the chest and abdominal cavities are separated by a diaphragm.

C2 - it is impossible, because the meeting of agglutinins β contained in the blood of group II with agglutinogens B contained in the blood of group III will lead to agglutination. There are no agglutinogens A and B in the blood of the group, so it can be transfused to all blood groups.

Criteria for evaluating responses

For each correctly completed task under the letter A, 1 point is awarded, a total of 7 points.

For each correctly completed task under the letter B, 2 points are awarded, a total of 10 points.

For each correctly completed task under the letter C, 3 points are awarded, a total of 6 points.

Total - 23 points

80-100% - rating "5"

60-80% - grade "4"

40-60% - grade "3"

0-40% - score "2".

Explanatory note

For the intermediate certification in biology in the 8th grade, a set of test tasks (2 options) was compiled. They are compiled taking into account the state educational standard. The content of the educational material is correlated with the amount of time allotted for the study of biology in the 8th grade by the basic curriculum (2 hours per week / 68 hours per year).

All questions and tasks are divided into three levels of difficulty (A, B, C).

Level A - basic (A1-A7). Each question has 4 possible answers, only one of which is correct.

Level B - contains 5 tasks (B1-B5). Each task of this level requires a short answer (in the form of one or two words).

Level C - increased complexity contains 2 tasks (C1-C2). This assignment requires you to write a detailed answer.

45 minutes are allotted to complete the test (1 lesson).

Final test for the academic year

Option 1

A1. What is the name of the science of the structure of man and his organs?

1) anatomy

2) physiology

3) biology

4) hygiene

A2. What part of the brain is called the small brain?

1) midbrain

2) spinal cord

3) medulla oblongata

4) cerebellum

A3. What muscle group do the temporalis muscles belong to?

1) to mimic

2) to chewing

3) to respiratory

4) to motor

A4. What is the name of the process of destruction of microbes by consuming cells?

1) immunity

2) brucellosis

3) phagocytosis

4) immunodeficiency

A5. What is the name of the enzyme of gastric juice that can only act in an acidic environment and breaks down protein into simpler compounds?

1) hemoglobin

2) pituitary gland

3) cerebellum

A6. What is the name of the nerve structures that convert perceived stimuli into nerve impulses?

1) sensitive neurons

2) receptors

3) intercalary neurons

4) synapses

IN 1. Establish the sequence of sections of the alimentary canal in humans.

A) small intestine

B) oral cavity

B) large intestine

D) stomach

E) esophagus

Answer: ________________________

IN 2. Choose the correct answer: What are the characteristics of therapeutic sera?

1) 1) are used to prevent infectious diseases

4) 4) antibodies do not last long in the body

5) 5) used to treat infectious diseases

Q 3. Choose the correct answer: What is the internal environment of the human body formed by?

6) tissue fluid

AT 4. Choose the correct answer: How is the human skeleton different from the skeleton of mammals?

1) spine without bends

2) arched foot

C1. What is the function of the respiratory organs?

C2. What is removed from the body through the kidneys?

Final for the academic year

Option 2

A1. What is the name of the warm salty liquid that connects all human organs with each other, providing them with oxygen and nutrition?

1) tissue fluid

4) intercellular substance

A2. Where does the division of the brain into right and left halves begin?

1) at the level of the cerebellum

2) at the level of the medulla oblongata

3) at the level of the midbrain

4) at the level of the spinal cord

A3. What type of tissue is bone tissue?

1) connective tissue

2) epithelial tissue

3) muscle tissue

4) nervous tissue

A4. What makes up the bulk of plasma?

3) erythrocytes

4) shaped elements

A5. What is the name of the largest gland in our body, located in the abdominal cavity under the diaphragm?

1) thyroid gland

2) spleen

3) pancreas

A6. What is the contact between neurons and cells of the working organs?

1) with the help of synapses

2) with the help of alveoli

3) using the vagus nerve

4) using receptors

IN 1. What are the characteristics of therapeutic serums?

1) are used to prevent infectious diseases

4) antibodies do not last long in the body

5)Used to treat infectious diseases

6) after the introduction cause diseases in a mild form

B2 Establish the sequence of sections of the alimentary canal in humans.

A) small intestine

B) oral cavity

B) large intestine

D) stomach

E) esophagus

Answer: |________________________

2. VZ. How is the human skeleton different from the skeleton of mammals?

1) spine without bends

2) arched foot

3) the spine is S-curved

4) the facial part of the skull prevails over the brain

5) the chest is compressed in the dorsal-abdominal direction

6) the ore cage is compressed laterally

AT 4. What is the internal environment of the human body?

2) organs of the chest and abdominal cavities

3) the contents of the stomach and intestines

4) cytoplasm, nucleus and organelles

6) tissue fluid

C1. name main criterion, which allows us to classify humans as mammals.

C2. How is the brain connected to the spinal cord?

Photo taken with an electron microscope showing the process of attaching bacteriophages (T1 coliphages) to the surface of an E. coli bacterium.

At the end of the 20th century, it became clear that bacteria undoubtedly dominate the Earth's biosphere, accounting for more than 90% of its biomass. Each species has many specialized types of viruses. According to preliminary estimates, the number of bacteriophage species is about 1015. To understand the scale of this figure, we can say that if every person on Earth discovers one new bacteriophage every day, then it will take 30 years to describe all of them. Thus, bacteriophages are the least studied creatures in our biosphere. Most of the bacteriophages known today belong to the order Caudovirales - tailed viruses. Their particles have a size of 50 to 200 nm. The tail of different lengths and shapes ensures the attachment of the virus to the surface of the host bacterium, the head (capsid) serves as a repository for the genome. Genomic DNA encodes the structural proteins that form the "body" of the bacteriophage and the proteins that ensure the multiplication of the phage inside the cell during infection. We can say that a bacteriophage is a natural high-tech nanoobject. For example, phage tails are a "molecular syringe" that pierces the wall of a bacterium and injects its DNA into the cell as it contracts.


Bacteriophages use the apparatus of a bacterial cell for reproduction, "reprogramming" it to produce new copies of viruses. The last step in this process is lysis, killing the bacterium and releasing new bacteriophages.


Photo taken with an electron microscope showing the process of attaching bacteriophages (T1 coliphages) to the surface of an E. coli bacterium.

All these molecular subtleties were not known in the second decade of the twentieth century, when "invisible infectious agents that destroy bacteria" were discovered. But even without the electron microscope, with which bacteriophages were first imaged in the late 1940s, it was clear that they were capable of destroying bacteria, including pathogens. This property was immediately demanded by medicine. The first attempts to treat dysentery, wound infections, cholera, typhoid and even plague with phages were carried out quite carefully, and the success looked quite convincing. But after the start of mass production and the use of phage preparations, euphoria turned into disappointment. Very little was known about what bacteriophages are, how to produce, purify and use their dosage forms. Suffice it to say that, according to the results of a test undertaken in the United States in the late 1920s, bacteriophages proper were not found in many industrial phage preparations.


The problem with antibiotics

The second half of the twentieth century in medicine can be called the “era of antibiotics”. However, Alexander Fleming, the discoverer of penicillin, warned in his Nobel lecture that microbial resistance to penicillin arises rather quickly. For the time being, antibiotic resistance has been offset by the development of new types of antimicrobial drugs. But since the 1990s, it has become clear that humanity is losing the “arms race” against microbes. First of all, the uncontrolled use of antibiotics is to blame, not only for therapeutic, but also for preventive purposes, and not only in medicine, but also in agriculture, food industry and everyday life. As a result, resistance to these drugs began to develop not only in pathogenic bacteria, but also in the most common microorganisms living in soil and water, making them “conditional pathogens”. Such bacteria comfortably exist in medical institutions, populating plumbing, furniture, medical equipment, and sometimes even disinfectant solutions. In people with weakened immune systems, which are the majority in hospitals, they cause severe complications.


bacteriophage is not creature, but a molecular nanomechanism created by nature. The tail of a bacteriophage is a syringe that pierces the wall of the bacterium and injects the viral DNA stored in the head (capsid) into the cell.

No wonder the medical community is sounding the alarm. Last year, WHO Director-General Margaret Chen issued a statement in 2012 predicting the end of the era of antibiotics and the vulnerability of humanity to infectious diseases. However, the practical possibilities of combinatorial chemistry - the foundations of pharmacological science - are far from being exhausted. Another thing is that the development of antimicrobial agents is a very expensive process that does not bring such profits as many other drugs. So the horror stories about “superbugs” are more of a warning that encourages people to look for alternative solutions.

In the medical service

It seems logical that there is a resurgence of interest in using bacteriophages, the natural enemies of bacteria, to treat infections. Indeed, during the decades of the “era of antibiotics”, bacteriophages actively served science, but not medicine, but fundamental science. molecular biology. Suffice it to mention the decoding of the "triplets" of the genetic code and the process of DNA recombination. Enough is now known about bacteriophages to reasonably select phages suitable for therapeutic purposes.


Bacteriophages have many advantages as potential drugs. First of all, there are a myriad of them. Although changing the genetic apparatus of a bacteriophage is also much easier than that of a bacterium, and even more so in higher organisms, That is unnecessary. You can always find something suitable in nature. It's about rather, about selection, fixing the properties in demand and reproduction of the necessary bacteriophages. This can be compared with the breeding of dog breeds - sledding, guard, hunting, hounds, fighting, decorative ... All of them remain dogs, but are optimized for a certain type of action, necessary to a person. Secondly, bacteriophages are strictly specific, that is, they destroy only a certain type of microbes, without inhibiting the normal human microflora. Thirdly, when a bacteriophage finds a bacterium that it must destroy, it begins to multiply during its life cycle. Thus, the question of dosage becomes not so acute. Fourth, bacteriophages do not cause side effects. All cases of allergic reactions when using therapeutic bacteriophages were caused either by impurities from which the drug was not sufficiently purified, or by toxins released during the mass death of bacteria. The last phenomenon, the "Herxheimer effect", is often observed with the use of antibiotics.


Two sides of the coin

Unfortunately, medical bacteriophages also have many shortcomings. The most important problem stems from the advantage - the high specificity of phages. Each bacteriophage infects a strictly defined type of bacteria, not even a taxonomic species, but a number of narrower varieties, strains. Relatively speaking, as if the guard dog started barking only at two-meter tall thugs dressed in black raincoats, and did not react at all to a teenager in shorts climbing into the house. Therefore, cases of ineffective use are not uncommon for current phage preparations. A drug made against a certain set of strains and perfectly treating streptococcal tonsillitis in Smolensk may be powerless against all signs of the same tonsillitis in Kemerovo. The disease is the same, caused by the same microbe, and streptococcus strains in different regions are different.

From the author

Since there are a myriad of bacteriophages in nature and they constantly enter the human body with water, air, food, the immune system simply ignores them. Moreover, there is a hypothesis about the symbiosis of bacteriophages in the intestine, which regulates the intestinal microflora. Some kind of immune reaction can be achieved only with prolonged administration of large doses of phages into the body. But in this way, you can achieve an allergy to almost any substance. Last but not least, bacteriophages are inexpensive. The development and production of a drug consisting of precisely selected bacteriophages with fully decoded genomes, cultivated according to modern biotechnological standards on certain bacterial strains in chemically pure media and highly purified, is orders of magnitude cheaper than for modern complex antibiotics. This makes it possible to quickly adapt phage therapeutic preparations to changing sets of pathogenic bacteria, as well as to use bacteriophages in veterinary medicine, where expensive drugs are not economically justified.

For the most effective use of a bacteriophage, an accurate diagnosis of a pathogenic microbe, down to a strain, is necessary. The most common diagnostic method now - culture seeding - takes a lot of time and does not provide the required accuracy. Rapid methods - typing using polymerase chain reaction or mass spectrometry - are slowly introduced due to the high cost of equipment and higher requirements for the qualifications of laboratory assistants. Ideally, the selection of phage components medicinal product could be done against the infection of each individual patient, but this is expensive and unacceptable in practice.

Another important disadvantage of phages is their biological nature. In addition to the fact that bacteriophages require special storage and transportation conditions to maintain infectivity, this method of treatment opens up scope for many speculations on the topic of "foreign DNA in humans." And although it is known that a bacteriophage, in principle, cannot infect a human cell and introduce its DNA into it, it is not easy to change public opinion. From the biological nature and rather large, in comparison with low-molecular drugs (the same antibiotics), the size follows the third limitation - the problem of delivering the bacteriophage into the body. If a microbial infection develops where a bacteriophage can be applied directly in the form of drops, spray or enema - on the skin, open wounds, burns, mucous membranes of the nasopharynx, ears, eyes, large intestine - then there are no problems.


But if the infection occurs in the internal organs, the situation is more complicated. Cases of successful treatment of infections of the kidneys or spleen with the usual oral administration of the bacteriophage preparation are known. But the very mechanism of penetration of relatively large (100 nm) phage particles from the stomach into the bloodstream and into internal organs poorly understood and varies greatly from patient to patient. Bacteriophages are also powerless against those microbes that develop inside cells, such as tuberculosis and leprosy. A bacteriophage cannot get through the wall of a human cell.

It should be noted that the use of bacteriophages and antibiotics for medical purposes should not be opposed. With their joint action, a mutual strengthening of the antibacterial effect is observed. This allows, for example, to reduce the doses of antibiotics to values ​​that do not cause pronounced side effects. Accordingly, the mechanism for the development of resistance in bacteria to both components of the combined drug is almost impossible. The expansion of the arsenal of antimicrobial drugs gives more degrees of freedom in the choice of treatment methods. Thus, the scientifically substantiated development of the concept of using bacteriophages in antimicrobial therapy is a promising direction. Bacteriophages serve not so much as an alternative, but as a complement and enhancement in the fight against infections.

What do you know about them?


At the end of the 20th century, it became clear that bacteria undoubtedly dominate the Earth's biosphere, accounting for more than 90% of its biomass. Each species has many specialized types of viruses. According to preliminary estimates, the number of bacteriophage species is about 10 to 15. To understand the scale of this figure, we can say that if every person on Earth discovers one new bacteriophage every day, then it will take 30 years to describe all of them. Thus, bacteriophages are the least studied creatures in our biosphere. Most of the bacteriophages known today belong to the order Caudovirales - tailed viruses.

Their particles have a size of 50 to 200 nm. The tail of different lengths and shapes ensures the attachment of the virus to the surface of the host bacterium, the head (capsid) serves as a repository for the genome. Genomic DNA encodes the structural proteins that form the "body" of the bacteriophage and the proteins that ensure the multiplication of the phage inside the cell during infection. We can say that a bacteriophage is a natural high-tech nanoobject. For example, phage tails are a "molecular syringe" that pierces the wall of a bacterium and injects its DNA into the cell as it contracts.


How bacteriophage works

Bacteriophages use the apparatus of a bacterial cell for reproduction, "reprogramming" it to produce new copies of viruses. The last step in this process is lysis, killing the bacterium and releasing new bacteriophages.

If there are not enough potential victims or the external conditions are not very suitable for the effective propagation of phages, then phages with a lysogenic development cycle will gain an advantage. In this case, after the introduction of the phage DNA into the bacterium, the infection mechanism does not immediately start, but for the time being it exists inside the cell in a passive state, often invading the bacterial genome. In this state of the prophage, the virus can exist for a long time, going through cell division cycles together with the bacterium's chromosome. And only when the bacterium enters an environment favorable for reproduction, the lytic cycle of infection is activated. At the same time, when phage DNA is released from the bacterial chromosome, neighboring regions of the bacterial genome are often captured, and their contents can later be transferred to next bacterium that the bacteriophage infects. This process (gene transduction) is considered the most important means transfer of information between prokaryotes - organisms without cell nuclei.



Photo taken with an electron microscope showing the process of attaching bacteriophages (T1 coliphages) to the surface of an E. coli bacterium.

All these molecular subtleties were not known in the second decade of the twentieth century, when "invisible infectious agents that destroy bacteria" were discovered. But even without the electron microscope, with which bacteriophages were first imaged in the late 1940s, it was clear that they were capable of destroying bacteria, including pathogens. This property was immediately demanded by medicine. The first attempts to treat dysentery, wound infections, cholera, typhoid and even plague with phages were carried out quite carefully, and the success looked quite convincing. But after the start of mass production and the use of phage preparations, euphoria turned into disappointment. Very little was known about what bacteriophages are, how to produce, purify and use their dosage forms. Suffice it to say that, according to the results of a test undertaken in the United States in the late 1920s, bacteriophages proper were not found in many industrial phage preparations.


The problem with antibiotics

The second half of the twentieth century in medicine can be called the “era of antibiotics”. However, Alexander Fleming, the discoverer of penicillin, warned in his Nobel lecture that microbial resistance to penicillin arises rather quickly. For the time being, antibiotic resistance has been offset by the development of new types of antimicrobial drugs. But since the 1990s, it has become clear that humanity is losing the “arms race” against microbes. First of all, the uncontrolled use of antibiotics is to blame, not only for therapeutic, but also for preventive purposes, and not only in medicine, but also in agriculture, the food industry and everyday life.

As a result, resistance to these drugs began to develop not only in pathogenic bacteria, but also in the most common microorganisms living in soil and water, making them “conditional pathogens”. Such bacteria comfortably exist in medical institutions, populating plumbing, furniture, medical equipment, and sometimes even disinfectant solutions. In people with weakened immune systems, which are the majority in hospitals, they cause severe complications.



A bacteriophage is not a living being, but a molecular nanomechanism created by nature. The tail of a bacteriophage is a syringe that pierces the wall of the bacterium and injects the viral DNA stored in the head (capsid) into the cell.

No wonder the medical community is sounding the alarm. In 2012, WHO Director-General Margaret Chan issued a statement predicting the end of the era of antibiotics and humanity's defenselessness against infectious diseases. However, the practical possibilities of combinatorial chemistry - the foundations of pharmacological science - are far from being exhausted. Another thing is that the development of antimicrobial agents is a very expensive process that does not bring such profits as many other drugs. So the horror stories about “superbugs” are more of a warning that encourages people to look for alternative solutions.

In the medical service

It seems logical that there is a resurgence of interest in using bacteriophages, the natural enemies of bacteria, to treat infections. Indeed, during the decades of the “era of antibiotics”, bacteriophages actively served science, not medicine, but fundamental molecular biology. Suffice it to mention the decoding of the "triplets" of the genetic code and the process of DNA recombination. Enough is now known about bacteriophages to reasonably select phages suitable for therapeutic purposes.

Bacteriophages have many advantages as potential drugs. First of all, there are a myriad of them. Although changing the genetic apparatus of a bacteriophage is also much easier than in a bacterium, and even more so in higher organisms, this is not necessary. You can always find something suitable in nature. Speech goes faster about selection, fixing of demanded properties and reproduction of the necessary bacteriophages. This can be compared with the breeding of dog breeds - sledding, guard, hunting, hounds, fighting, decorative ... All of them remain dogs, but are optimized for a certain type of action that a person needs. Secondly, bacteriophages are strictly specific, that is, they destroy only a certain type of microbes, without inhibiting the normal human microflora. Thirdly, when a bacteriophage finds a bacterium that it must destroy, it begins to multiply during its life cycle. Thus, the question of dosage becomes not so acute. Fourth, bacteriophages do not cause side effects. All cases of allergic reactions when using therapeutic bacteriophages were caused either by impurities from which the drug was not sufficiently purified, or by toxins released during the mass death of bacteria. The last phenomenon, the "Herxheimer effect", is often observed with the use of antibiotics.

Two sides of the coin.

Unfortunately, medical bacteriophages also have many shortcomings. The most important problem stems from the advantage - the high specificity of phages. Each bacteriophage infects a strictly defined type of bacteria, not even a taxonomic species, but a number of narrower varieties, strains. Relatively speaking, as if the guard dog started barking only at two-meter tall thugs dressed in black raincoats, and did not react at all to a teenager in shorts climbing into the house. Therefore, cases of ineffective use are not uncommon for current phage preparations. A drug made against a certain set of strains and perfectly treating streptococcal tonsillitis in Smolensk may be powerless against all signs of the same tonsillitis in Kemerovo. The disease is the same, caused by the same microbe, and streptococcus strains in different regions are different.

Konstantin Miroshnikov:
Since there are a myriad of bacteriophages in nature and they constantly enter the human body with water, air, food, the immune system simply ignores them. Moreover, there is a hypothesis about the symbiosis of bacteriophages in the intestine, which regulates the intestinal microflora. Some kind of immune reaction can be achieved only with prolonged administration of large doses of phages into the body. But in this way, you can achieve an allergy to almost any substance. Last but not least, bacteriophages are inexpensive. The development and production of a drug consisting of precisely selected bacteriophages with fully decoded genomes, cultivated according to modern biotechnological standards on certain bacterial strains in chemically pure media and highly purified, is orders of magnitude cheaper than for modern complex antibiotics. This makes it possible to quickly adapt phage therapeutic preparations to changing sets of pathogenic bacteria, as well as to use bacteriophages in veterinary medicine, where expensive drugs are not economically justified.

For the most effective use of a bacteriophage, an accurate diagnosis of a pathogenic microbe, down to a strain, is necessary. The most common diagnostic method now - culture seeding - takes a lot of time and does not provide the required accuracy. Rapid methods - typing using polymerase chain reaction or mass spectrometry - are slowly introduced due to the high cost of equipment and higher requirements for the qualifications of laboratory assistants. Ideally, the selection of phage components of the drug could be done against the infection of each individual patient, but this is expensive and unacceptable in practice.

Another important disadvantage of phages is their biological nature. In addition to the fact that bacteriophages require special storage and transportation conditions to maintain infectivity, this method of treatment opens up scope for many speculations on the topic of "foreign DNA in humans." And although it is known that a bacteriophage, in principle, cannot infect a human cell and introduce its DNA into it, it is not easy to change public opinion. From the biological nature and rather large, in comparison with low-molecular drugs (the same antibiotics), the size follows the third limitation - the problem of delivering the bacteriophage into the body. If a microbial infection develops where a bacteriophage can be applied directly in the form of drops, spray or enema - on the skin, open wounds, burns, mucous membranes of the nasopharynx, ears, eyes, large intestine - then there are no problems.

But if the infection occurs in the internal organs, the situation is more complicated. Cases of successful treatment of infections of the kidneys or spleen with the usual oral administration of the bacteriophage preparation are known. However, the mechanism of penetration of relatively large (100 nm) phage particles from the stomach into the bloodstream and into the internal organs is poorly understood and varies greatly from patient to patient. Bacteriophages are also powerless against those microbes that develop inside cells, such as tuberculosis and leprosy. A bacteriophage cannot get through the wall of a human cell.

It should be noted that the use of bacteriophages and antibiotics for medical purposes should not be opposed. With their joint action, a mutual strengthening of the antibacterial effect is observed. This allows, for example, to reduce the doses of antibiotics to values ​​that do not cause pronounced side effects. Accordingly, the mechanism for the development of resistance in bacteria to both components of the combined drug is almost impossible. The expansion of the arsenal of antimicrobial drugs gives more degrees of freedom in the choice of treatment methods. Thus, the scientifically substantiated development of the concept of using bacteriophages in antimicrobial therapy is a promising direction.

Bacteriophages serve not so much as an alternative, but as a complement and enhancement in the fight against infections.

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