The mechanism of action of antibiotics: a detailed description

It can be said that the revolutionary event was the discovery of penicillin at the beginning of the last century. During the Second World War, the first antibiotic saved millions of wounded soldiers from sepsis. Penicillin has become effective and at the same time a cheap drug for many serious infections with serious fractures, purulent wounds. Over time, other classes of antibiotics were synthesized.

General characteristics of

Today, there are already a large number of drugs related to the vast world of antibiotics - substances of natural or semi-synthetic origin that have the ability to kill certain groups of pathogens or hinder their growth or reproduction. Mechanisms, the spectra of antibiotics can be different. Over time, new types and modifications of antibiotics are emerging. Such a diversity requires systematization. In our time, the classification of antibiotics according to the mechanism and spectrum of action, as well as the chemical structure, has been adopted. By the mechanism of action, they are divided into:

• bacteriostatic, inhibiting the growth or multiplication of pathogenic microorganisms;
• bactericidal, which contribute to the destruction of bacteria.

Basic mechanisms of action of antibiotics:

• infringement of bacterial cell wall;
• suppression of protein synthesis in a microbial cell;
• violation of the permeability of the cytoplasmic membrane;
• inhibition of RNA synthesis.

Beta-lactams - penicillins

By chemical structure, these compounds are subdivided as follows.

Beta-lactam antibiotics. The mechanism of action of lactam antibiotics is determined by the ability of this functional group to bind enzymes involved in the synthesis of peptidoglycan - the basis of the outer membrane of microorganism cells. Thus, the formation of its cell wall is inhibited, which helps to stop the growth or multiplication of bacteria. Beta-lactams have low toxicity and at the same time a good bactericidal effect. They represent the largest group and are divided into subgroups having a similar chemical structure.

Penicillins are a group of substances released from a specific colony of molds and active bactericidal. The mechanism of action of antibiotics of the penicillin series is due to the fact that by destroying the cellular wall of microorganisms, they destroy them. Penicillins are of natural and semi-synthetic origin and are compounds of a wide spectrum of action - they can be used in the treatment of many diseases caused by streptococci and staphylococci. In addition, they have the property of selectivity, acting only on microorganisms, without affecting the macroorganism. Penicillins have their drawbacks, which include the emergence of resistance to bacteria. Of natural most common are benzylpenicillin, phenoxymethylpenicillin, which are used to fight meningococcal and streptococcal infections due to low toxicity and low cost. However, with long-term admission, there may be an organism's immunity to the drug, which will lead to a decrease in its effectiveness. Semisynthetic penicillins are usually obtained from natural by chemical modification to give them the right properties - amoxicillin, ampicillin. These drugs are more active against bacteria that are resistant to bio-penicillins.

Other beta-lactams

Cephalosporins are obtained from fungi of the same name, and their structure is similar to the structure of penicillins, which explains the same negative reactions. Cephalosporins are four generations old. First-generation drugs are used more often in the treatment of mild forms of infections caused by staphylococci or streptococci. The second and third generation of cephalosporins are more active against gram-negative bacteria, and substances of the fourth generation are the strongest drugs used to influence severe infections.

Carbapenems effectively act on gram-positive, gram-negative and anaerobic bacteria. Their positive property is the lack of bacterial resistance to the drug even after a long period of use.

Monobactams also belong to beta-lactams and have a similar mechanism of action of antibiotics, which consists in the effect on the cell walls of bacteria. They are used to treat a variety of infections.

Macrolides

This is the second group. Macrolides are natural antibiotics that have a complex cyclic structure. They are a polynomial lactone ring with attached carbohydrate residues. The properties of the drug depend on the amount of carbon atoms in the ring. There are 14-, 15- and 16-membered compounds. The spectrum of their action on microbes is wide enough. The mechanism of action of antibiotics on a microbial cell consists in their interaction with ribosomes and thereby breaking the synthesis of proteins in the cell of the microorganism by suppressing the reactions of attachment of new monomers to the peptide chain. Accumulating in the cells of the immune system, macrolides also carry out intracellular destruction of microbes.

Macrolides are the safest and less toxic among known antibiotics and are effective against not only gram-positive, but also gram-negative bacteria. When they are used, undesirable side reactions are not observed. These antibiotics are characterized by bacteriostatic action, but at high concentrations are able to have a bactericidal effect on pneumococci and some other microorganisms. By the method of production macrolides are divided into natural and semi-synthetic.

The first drug from the class of natural macrolides was erythromycin, obtained in the middle of the last century and successfully used against gram-positive bacteria, resistant against penicillins. A new generation of drugs of this group appeared in the 70s of the 20th century and is actively used till now.

Macrolides also include semi-synthetic antibiotics - azolid and ketolide. In the azolide molecule, a nitrogen atom is included in the lactone ring between the ninth and tenth carbon atoms. The representative of azolides is azithromycin of a broad spectrum of action and activity in the direction of gram-positive and gram-negative bacteria, some anaerobes. It is much more stable in acidic medium, in comparison with erythromycin, and can accumulate in it. Azithromycin is used for a variety of diseases of the respiratory tract, urogenital system, intestines, skin and others.

Ketolides are obtained by attaching to the third atom a lactone ring of the keto group. They are distinguished by less addictive bacteria, when compared with macrolides.

Tetracyclines

Tetracyclines belong to the class of polyketides. They are antibiotics of a wide spectrum of action, possessing bacteriostatic influence. The first representative of them - chlorotetracycline, was isolated in the middle of the last century from one of the cultures of actinomycetes, they are also called radiant fungi. A few years later oxytetracycline was obtained from a colony of the same fungi. The third representative of this group is tetracycline, which was first created by chemical modification of its chloro derivative, and a year later also isolated from actinomycetes. All other preparations of the tetracycline group are semisynthetic derivatives of these compounds.

All these substances are similar in chemical structure and properties, in activity against many forms of gram-positive and gram-negative bacteria, certain viruses and protozoa. They are also resistant to microbial addiction. The mechanism of action of antibiotics on the bacterial cell is to suppress the processes of protein biosynthesis in it. When the molecules of the drug act on gram-negative bacteria they pass into the cell by simple diffusion. The mechanism of penetration of antibiotic particles into gram-positive bacteria has not been sufficiently studied, however, it is suggested that tetracycline molecules interact with ions of certain metals that are in bacterial cells to form complex compounds. This breaks the chain during the formation of protein, necessary for the bacterial cell. Experiments have shown that bacteriostatic concentrations of chlorotetracycline are sufficient to suppress protein synthesis, however, large concentrations of the drug are required to inhibit the synthesis of nucleic acids.

Tetracyclines are used in the fight against kidney disease, various infections of the skin, respiratory tract and many other diseases. If necessary, they replace penicillin, but in recent years the use of tetracyclines has decreased markedly, which is associated with the emergence of resistance of microorganisms to this group of antibiotics. The negative role played by the use of this antibiotic as an additive to animal feed, which led to a decrease in the medicinal properties of the drug due to the emergence of resistance to it. To overcome it, combinations with different drugs with a different mechanism of antimicrobial action of antibiotics are prescribed. For example, the therapeutic effect is enhanced by the simultaneous use of tetracycline and streptomycin.

Aminoglycosides

Aminoglycosides are natural and semi-synthetic antibiotics with an extremely wide spectrum of action, containing in the molecule the remains of amino sugars. The first aminoglycoside was streptomycin, isolated from a colony of radiant fungi already in the middle of the last century and was actively used in the treatment of a variety of infections. Being bactericidal, the antibiotics of this group are effective even with greatly reduced immunity. The mechanism of action of antibiotics on the microbial cell consists in the formation of strong covalent bonds with the ribosome proteins of the microorganism and the destruction of the protein synthesis reactions in the bacterial cell. Until the end, the mechanism of the bactericidal effect of aminoglycosides has not been studied, in contrast to the bacteriostatic effect of tetracyclines and macrolides, which also violate protein synthesis in bacterial cells. However, it is known that aminoglycosides are active only under aerobic conditions, therefore they show low efficiency in tissues with weak blood supply.

After the appearance of the first antibiotics - penicillin and streptomycin, they began to be so widely used in the treatment of any diseases that very soon arose the problem of microorganisms getting used to these medicines. Currently, streptomycin is used, mainly in combination with other drugs of the new generation for the treatment of tuberculosis or such, to date, rare infections like the plague. In other cases, kanamycin is prescribed, which is also an antibiotic of the first generation of aminoglycosides. However, due to the high toxicity of kanamycin, gentamicin is now the preferred drug, the second generation, and the third generation aminoglycoside is amikacin, which is used rarely to prevent microorganisms from becoming addicted to it.

Levomycetin

Levomycetin, or chloramphenicol, is a natural antibiotic with a broad spectrum of action, active against a significant number of gram-positive and gram-negative microorganisms, many large viruses. According to the chemical structure, this derivative of nitrophenylalkylamines was first obtained from the culture of actinomycetes in the middle of the 20th century, and two years later it was also synthesized chemically.

Levomycetin has a bacteriostatic effect on microorganisms. The mechanism of action of antibiotics on the bacterial cell is to suppress the activity of the catalysts of the formation of peptide bonds in the ribosomes during protein synthesis. Resistance to levomycetin in bacteria develops very slowly. The drug is used for typhoid fever or dysentery.

Glycopeptides and lipopeptides

Glycopeptides are cyclic peptide compounds that are natural or semi-synthetic antibiotics with a narrow spectrum of action on certain strains of microorganisms. They have a bactericidal effect on Gram-positive bacteria, and can also replace penicillin in the event of resistance to it. The mechanism of action of antibiotics on microorganisms can be explained by the formation of bonds with peptidoglycan amino acids of the cell wall and, thus, suppression of their synthesis.

The first glycopeptide, vancomycin, was derived from actinomycetes taken from soil in India. It is a natural antibiotic that actively acts on microorganisms even during the breeding season. Initially, vancomycin was used as a substitute for penicillin in cases of allergy to it in the treatment of infections. However, the increase in resistance to the drug has become a serious problem. In the 80s, teicoplanin, an antibiotic from the glycopeptide group, was obtained. He is prescribed for the same infections, and in combination with gentamicin he gives good results.

At the end of the 20th century a new group of antibiotics appeared - lipopeptides isolated from streptomycetes. According to their chemical structure, they are cyclic lipopeptides. These are antibiotics with a narrow spectrum of action, showing a bactericidal effect against Gram-positive bacteria, as well as staphylococci, resistant to beta-lactam drugs and glycopeptides.

The mechanism of action of antibiotics differs significantly from the already known ones - the lipopeptide forms strong bonds with the cell membrane of bacteria in the presence of calcium ions, which lead to its depolarization and disruption of protein synthesis, as a result of which the harmful cell dies. The first representative of the class of lipopeptides is daptomycin.

With respect to daptomycin, a significant rate of bactericidal activity can be noted, and most importantly - the absence of cross resistance or, at least, its very slow formation, due to the fact that a completely new mechanism of action of antibiotics is incorporated in the structure of this substance.

Polyenes

The next group is polyene antibiotics. Today there is a huge surge of fungal diseases that are difficult to treat. To combat them, antifungal agents are intended - natural or semi-synthetic polyene antibiotics. The first antifungal drug in the middle of the last century was nystatin, which was isolated from the culture of streptomycetes. During this period, many polyene antibiotics obtained from various fungal cultures - griseofulvin, levorin and others - were included in medical practice. Now the fourth-generation polyenes have been used. They got the general name due to the presence of several double bonds in the molecules.

The mechanism of action of polyene antibiotics is due to the formation of chemical bonds with sterols of cell membranes in the fungus. The polyene molecule is thus embedded in the cell membrane and forms an ionic wire channel through which the components of the cell go out, leading to its elimination. In small doses polyenes are fungistatic, and in high doses fungicidal. However, their activity does not extend to bacteria and viruses.

Polymyxins - natural antibiotics, are produced by soil spore-forming bacteria. In therapy, they found application in the 40s of last century. These drugs are characterized by bactericidal action, which is caused by damage to the cytoplasmic membrane of the microorganism cell causing its death. Polymyxins are effective against gram-negative bacteria and rarely cause microorganisms to become addictive. However, too high toxicity limits their use in therapy. The compounds of this group - polymyxin B sulfate and polymyxin M sulfate are used rarely and only as a reserve preparation.

Antineoplastic antibiotics

Actinomycins are produced by some radiant fungi, exerting cytostatic action. Natural actinomycins in structure are chromopeptides, differing in amino acids in peptide chains, determining their biological activity. Actinomycins attract the attention of specialists as antitumor antibiotics. The mechanism of their action is due to the formation of sufficiently stable bonds of the peptide chains of the preparation with a double helix of the DNA of the microorganism and the blocking due to this synthesis of RNA.

Dactinomycin, obtained in the 1960s, became the first antitumor drug found in oncological therapy. However, due to the large number of side effects this drug is rarely used. More active antitumor drugs have now been obtained.

Anthracyclines are extremely strong antitumour substances isolated from streptomycetes. The mechanism of action of antibiotics is associated with the formation of triple complexes with DNA strands and rupture of these chains. A second mechanism of antimicrobial action is also possible, due to the production of free radicals that oxidize cancer cells.

Among natural anthracyclines, daunorubicin and doxorubicin can be mentioned. The classification of antibiotics according to the mechanism of action on bacteria classifies them as bactericidal. However, their high toxicity caused them to look for new compounds that were obtained synthetically. Many of them are successfully used in oncology.

Antibiotics have long been involved in medical practice and human life. Thanks to them, many diseases were defeated, which for many centuries were considered incurable. At present, there is such a variety of these compounds that it is required not only the classification of antibiotics according to the mechanism and the spectrum of the action, but also on many other characteristics.