All the microscopic enemies of the human race have been declared at war to the death. It is still being conducted with varying success, but some diseases have already receded, it seems, forever, for example, smallpox. But at the same time, there is still smallpox of camels, cows, and also smallpox of monkeys. However, smallpox is not so simple. No cases of smallpox have been reported since the mid-1980s. In this regard, children have not been vaccinated against smallpox for quite a long time. Thus, in the human population, the number of people resistant to the smallpox virus decreases every year. And this virus has not gone away. It can be preserved on the bones of people who died from smallpox (not all the corpses were burned, some of them had no one to burn them) for as long as you want.
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And someday there will definitely be a meeting of an unvaccinated person, for example, an archaeologist, with a virus. Many previously fatal diseases – dysentery, cholera, purulent infections, pneumonia, etc. – have faded into the background. However, sap, which has not been observed for almost 100 years, seems to have returned. A number of countries are experiencing outbreaks of polio after decades that have passed without this terrible disease. New threats have been added, in particular avian flu. The avian flu virus is already killing predatory mammals. Open borders have made it impossible to fight microbes in a single state. If previously there were diseases that are more characteristic of a particular region, then at the moment even the boundaries of climatic zones that are more characteristic of a particular type of pathology are blurred. Of course, specific infections of the tropical zone do not yet threaten the inhabitants of the Far North, but, for example, sexual infections, AIDS, hepatitis B, C as a result of the process of universal globalization have become a truly global threat. Malaria has spread from hot countries all the way to the Arctic Circle.
The cause of classical infectious diseases is pathogenic microorganisms represented by bacteria (such as bacilli, cocci, spirochetes, rickettsias), viruses of a number of families (herpesviruses, adenoviruses, papovaviruses, parvoviruses, orthomyxoviruses, paramyxoviruses, retroviruses, bunyaviruses, togaviruses, coronaviruses, picornaviruses, arenoviruses and rhabdoviruses), fungi (oomycetes, ascomycetes, actinomycetes, basidiomycetes, deuteromycetes) and protozoa (flagellates, sarcodes, spores, ciliates). In addition to pathogenic microorganisms, there is a large group of conditionally pathogenic microbes that can provoke the development of so – called opportunistic infections-a pathological process in people with various immunodeficiencies. Since the possibility of obtaining antibiotic drugs from microorganisms was clearly proved, the discovery of new drugs became a matter of time. It usually turns out that time does not work for doctors and microbiologists, but, on the contrary, for representatives of the pathogenic microflora. However, at first there was even a reason for optimism. In 1939. gramicidin was isolated, followed in chronological order by streptomycin (in 1942), chlortetracycline (in 1945), levomycetin (in 1947), and by 1950 more than 100 antibiotics had been described. It should be noted that in the 1950s and 1960s, this caused premature euphoria in medical circles. In 1969, a very optimistic report was presented to the US Congress, containing such bold statements as “the book of infectious diseases will be closed”. One of the most widespread mistakes of mankind is an attempt to overtake the natural evolutionary process, because man is only a part of this process. The search for new antibiotics is a very long, painstaking process that requires serious funding. Many antibiotics have been isolated from microorganisms whose habitat is soil. It turned out that in the soil live the deadly enemies of a number of pathogenic microorganisms for humans-pathogens of typhus, cholera, dysentery, tuberculosis, etc. Streptomycin, used to treat tuberculosis to date, has also been isolated from soil microorganisms. In order to select the desired strain, z. Waxman (the discoverer of streptomycin) studied over 500 crops for 3 years before finding a suitable one – one that releases more streptomycin into the habitat than other crops. In the course of scientific research, many thousands of cultures of microorganisms are carefully studied and rejected. And only a few instances are used for further study. However, this does not mean that all of them will then become a source for obtaining new medicines. The extremely low productivity of crops, the technical complexity of the isolation and subsequent purification of medicinal substances pose additional, often insurmountable barriers to new drugs. And new antibiotics are as necessary as air. Who could have imagined that the viability of microbes would become such a serious problem? In addition, new pathogens of infectious diseases were detected, and the range of activity of existing drugs became insufficient for effective control of them. The microorganisms adapted very quickly and became immune to the action of seemingly already proven drugs. It was quite possible to foresee the emergence of drug resistance of microbes, and it is not necessary to be a talented science fiction writer for this. Rather, the role of brilliant visionaries should have been played by skeptics from the scientific community. But if someone predicted something like this, his voice was not heard, his opinion was not taken into account. But a similar situation was already observed with the introduction of the insecticide DDT in the 1940s. At first, the flies, against which such a massive attack was launched, almost completely disappeared, but then they multiplied in huge numbers, and the new generation of flies was resistant to DDT, which indicates the genetic consolidation of this trait. As for microorganisms, A. Fleming also found that subsequent generations of staphylococci formed cell walls with a structure resistant to the effects of penicillin. More than 30 years ago, Academician S. Schwartz warned about the state of affairs that can develop with such a vector of development of events. He said: “No matter what happens on the upper floors of nature, no matter what cataclysms shake the biosphere… the highest efficiency of energy use at the level of cells and tissues guarantees life to organisms that will restore life on all its floors in the form that corresponds to the new environmental conditions.” Some bacteria can reject antibiotics as they enter or neutralize them. For this reason, in parallel with the search for new types of natural antibiotics, in-depth work was carried out to analyze the structure of already known substances, in order to then, based on this data, modify them, creating new, much more effective and safe drugs. A new stage in the evolution of antibiotics, of course, was the invention and introduction into medical practice of semi-synthetic drugs that are similar in structure or in the type of exposure to natural antibiotics. In 1957. for the first time, it was possible to isolate phenoxymethylpenicillin, resistant to the action of hydrochloric acid in gastric juice, which can be taken in tablet form. Penicillins of natural origin were completely ineffective when taken orally, as they lost their activity in the acidic environment of the stomach.
Later, a method for producing semi-synthetic penicillins was invented. For this purpose, the penicillin molecule was ” cut ” by the action of the enzyme penicillinase and, using one of the parts, new compounds were synthesized. Using this technique, it was possible to create drugs of a much wider spectrum of antimicrobial action (amoxicillin, ampicillin, carbenicillin) than the original penicillin. An equally well-known antibiotic, cephalosporin, was first isolated in 1945. from sewage on the island of Sardinia, he became the founder of a new group of semi-synthetic antibiotics – cephalosporins, which have a powerful antibacterial effect and are almost harmless to humans. There are already more than 100 different cephalosporins. Some of them can destroy both Gram-positive and gram-negative microorganisms, while others act on resistant strains of bacteria. It is clear that any antibiotic has its own specific selective effect on strictly defined types of microorganisms. Due to this selective action, a significant part of antibiotics is able to nullify many types of pathogenic microorganisms, acting in harmless or almost harmless concentrations for the body. It is this type of antibiotic drugs that are extremely often and widely used to treat a variety of infectious diseases. The main sources that are used for the production of antibiotics are microorganisms with a habitat in the soil and water, where they continuously interact, entering into a variety of relationships that can be neutral, antagonistic or mutually beneficial. A striking example is putrefactive bacteria, which create good conditions for the normal functioning of nitrifying bacteria. However, often the relationships of microorganisms are antagonistic, i.e. directed against each other. This is quite understandable, since only in this way could the ecological balance of a huge number of biological forms be initially maintained in nature. The Russian scientist I. I. Mechnikov, far ahead of his time, was the first to suggest the practical application of antagonism between bacteria. He advised to suppress the vital activity of putrefactive bacteria, which constantly live in the human intestine, at the expense of useful lactic acid bacteria; the products of vital activity released by putrefactive microbes, according to the scientist, shorten human life. There are various types of antagonism (counteraction) of microbes.
All of them are associated with competition for oxygen and nutrients and are often accompanied by a change in the acid-base balance of the environment in the direction that is optimally suitable for the vital activity of one type of microorganisms, but unfavorable for its competitor. At the same time, one of the most universal and effective mechanisms for the manifestation of microbial antagonism is the production of various chemicals-antibiotics. These substances can either inhibit the growth and reproduction of other microorganisms (bacteriostatic action), or destroy them (bactericidal action). Bacteriostatic agents include antibiotics such as erythromycin, tetracyclines, and aminoglycosides. Bactericidal drugs cause the death of microorganisms, the body can only cope with the elimination of their waste products. These are penicillin-type antibiotics, cephalosporins, carbapenems, etc. Some antibiotics that act bacteriostatically destroy microorganisms if used in high concentrations (aminoglycosides, levomycetin). But you should not get carried away with increasing the dose, since with an increase in concentration, the probability of a toxic effect on human cells increases dramatically. What is the mechanism of action of antibiotics? In many antimicrobial agents, it is not completely clarified. However, it is safe to say that the effect of most antibiotics is to disrupt the normal permeability of the cell membrane and inhibit the formation of substances that form the basis of the structure of the cell walls of bacteria or protein inside the cell. In the first case, the metabolism between the microorganism and the external environment suffers. In the second case, the cell, losing its shell, dissolves in its habitat and ceases to exist as a biological unit. In the third variant, a violation of protein synthesis leads to a slowdown in vital activity, the microorganism seems to fall asleep. In any case, the microbe ceases to produce toxins and, therefore, no longer poses a threat to humans. There are a number of requirements for modern antibiotics, so that they can be considered good therapeutic drugs. Some of them have already been mentioned above. So, modern antibiotics should:
“Already in a low concentration (10-30 micrograms/ml), destroy the pathogenic microorganism or significantly suppress its growth and reproduction. The activity of the antibiotic should not significantly decrease under the influence of biological fluids;
“Quickly affect the microorganism in order to interrupt its life cycle in a short time;”
“Be harmless to the macroorganism, i.e. to the human being. Such effects as allergenicity and toxicity are completely unacceptable both after a single dose and after repeated administration. Antibiotics should not interfere with the recovery process, reduce and even more so suppress immunological reactions, damage the body’s immune system. However, there are no rules without exceptions, and these exceptions only confirm the rules. The search for antibiotic drugs that could suppress normal transplant immunity has long been underway, thereby greatly expanding the possibilities of modern transplantology. These include cyclosporine A, which is a fairly strong immunosuppressant (a means that suppresses the natural human immune system), but its widespread use is hindered, unfortunately, by the cytotoxic effect on the kidneys. According to the selectivity of their effects, all antibiotics can be divided into several main groups.”
A number of researchers refer to antibiotics not only chemicals that are formed as a result of the vital activity of microorganisms, but also synthetic compounds obtained by chemical methods, rightly believing that it is not so much the method of obtaining the drug, but the degree of its antimicrobial activity and usefulness for humans.
Scientists, after numerous experiments and studies, came to a stunning conclusion: it turned out that new strains are born from already known microbes, for the treatment of which the invention of new drugs is required.