It can be said that the discovery of penicillin at the beginning of the last century was a revolutionary event. During World War II, the first antibiotic saved millions of wounded soldiers from sepsis. Penicillin has become an effective and at the same time cheap drug for many serious infections with serious fractures, purulent wounds. Over time, other classes of antibiotics were synthesized.
General characteristics
Today, there are already a large number of drugs belonging to the vast world of antibiotics - substances of natural or semi-synthetic origin that have the ability to destroy certain groups of pathogens or prevent their growth or reproduction. Mechanisms, spectra of action of antibiotics can be different. Over time, new types and modifications of antibiotics appear. Their 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 accepted. According to the mechanism of action, they are divided into:
- bacteriostatic, growth inhibiting orreproduction of pathogenic microorganisms;
- bactericidal, which help kill bacteria.
Basic mechanisms of action of antibiotics:
- violation of the 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 classified 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 suppressed, which helps to stop the growth or reproduction of bacteria. Beta-lactams have low toxicity and at the same time good bactericidal action. They represent the largest group and are divided into subgroups that have a similar chemical structure.
Penicillins are a group of substances isolated from a certain colony of molds and acting bactericidal. The mechanism of action of antibiotics of the penicillin series is due to the fact that, destroying the cell wall of microorganisms, they destroy them. Penicillins are of natural and semi-synthetic origin and are broad-spectrum compounds - they can be used in the treatment of many diseases caused by streptococci and staphylococci. Besides,they have the property of selectivity, acting only on microorganisms, without affecting the macroorganism. Penicillins have their drawbacks, which include the emergence of bacterial resistance to it. Of the natural, the most common are benzylpenicillin, phenoxymethylpenicillin, which are used to combat meningococcal and streptococcal infections due to low toxicity and low cost. However, with long-term use, the body's immunity to the drug may occur, which will lead to a decrease in its effectiveness. Semi-synthetic penicillins are usually obtained from natural ones by chemical modification to give them the desired properties - amoxicillin, ampicillin. These drugs are more active against bacteria resistant to biopenicillins.
Other beta-lactams
Cephalosporins are obtained from mushrooms of the same name, and their structure is similar to the structure of penicillins, which explains the same negative reactions. Cephalosporins make up four generations. First-generation drugs are used more often in the treatment of mild infections caused by staphylococci or streptococci. Second and third generation cephalosporins are more active against gram-negative bacteria, and fourth generation substances are the most powerful drugs used to treat severe infections.
Carbapenems are effective against Gram-positive, Gram-negative and anaerobic bacteria. Their advantage is the absenceresistance of bacteria to the drug even after prolonged use.
Monobactams also belong to beta-lactams and have a similar mechanism of action of antibiotics, which consists in influencing the cell walls of bacteria. They are used to treat a wide variety of infections.
Macrolides
This is the second group. Macrolides are natural antibiotics with a complex cyclic structure. They are a multi-membered lactone ring with attached carbohydrate residues. The properties of the drug depend on the number of carbon atoms in the ring. There are 14-, 15- and 16-membered compounds. The spectrum of their action on microbes is quite wide. The mechanism of action of antibiotics on the microbial cell consists in their interaction with ribosomes and thereby disrupting the synthesis of proteins in the cell of the microorganism by suppressing the reactions of adding 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 least toxic among known antibiotics and are effective against not only Gram-positive but also Gram-negative bacteria. When using them, undesirable side reactions are not observed. These antibiotics are characterized by a bacteriostatic effect, but at high concentrations they can have a bactericidal effect on pneumococci and some other microorganisms. According to the method of preparation, macrolides are divided into natural and semi-synthetic.
The first drug fromA class of natural macrolides was erythromycin, obtained in the middle of the last century and successfully used against gram-positive bacteria resistant to penicillins. A new generation of drugs in this group appeared in the 70s of the 20th century and is still actively used.
Macrolides also include semi-synthetic antibiotics - azolides and ketolides. 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 with a wide spectrum of action and activity in the direction of gram-positive and gram-negative bacteria, some anaerobes. It is much more stable in an acidic environment than erythromycin, and can accumulate in it. Azithromycin is used for a variety of diseases of the respiratory tract, genitourinary system, intestines, skin and others.
Ketolides are obtained by adding a keto group to the third atom of the lactone ring. They are distinguished by less habituation of bacteria when compared with macrolides.
Tetracyclines
Tetracyclines belong to the class of polyketides. These are broad-spectrum antibiotics with a bacteriostatic effect. Their first representative, chlortetracycline, 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 chlorine derivative, and a year later also isolated from actinomycetes. Otherdrugs of the tetracycline group are semi-synthetic 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, some viruses and protozoa. They are also resistant to the habituation of microorganisms. The mechanism of action of antibiotics on a bacterial cell is to suppress the processes of protein biosynthesis in it. When drug molecules 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 yet been sufficiently studied, however, there is an assumption that tetracycline molecules interact with certain metal ions that are in bacterial cells to form complex compounds. In this case, the chain breaks in the process of formation of the protein necessary for the bacterial cell. Experiments have shown that bacteriostatic concentrations of chlortetracycline are sufficient to suppress protein synthesis, however, high 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 microbial resistance to this group of antibiotics. The use of thisantibiotic 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 that have 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 aminosaccharide residues in the molecule. The first aminoglycoside was streptomycin, isolated from a colony of radiant fungi already in the middle of the last century and actively used in the treatment of many infections. Being bactericidal, the antibiotics of the mentioned group are effective even with severely reduced immunity. The mechanism of action of antibiotics on a microbial cell is the formation of strong covalent bonds with the proteins of the ribosomes of the microorganism and the destruction of protein synthesis reactions in the bacterial cell. The mechanism of the bactericidal effect of aminoglycosides has not been fully studied, in contrast to the bacteriostatic effect of tetracyclines and macrolides, which also disrupt protein synthesis in bacterial cells. However, aminoglycosides are known to be active only under aerobic conditions, so they are not very effective in tissues with poor 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 the problem of microorganisms getting used to these drugs arose. CurrentlyStreptomycin is mainly used in combination with other newer drugs to treat tuberculosis or rare infections such as plague. In other cases, kanamycin is prescribed, which is also a first-generation aminoglycoside antibiotic. However, due to the high toxicity of kanamycin, gentamicin, a second-generation drug, is now preferred, and the third-generation aminoglycoside drug is amikacin, which is rarely used to prevent microorganisms from becoming addicted to it.
Levomycetin
Levomycetin, or chloramphenicol, is a natural antibiotic with the widest spectrum of activity, 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 a 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 a bacterial cell is to suppress the activity of catalysts for the formation of peptide bonds in ribosomes during protein synthesis. Bacterial resistance to levomycetin 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 narrowspectrum 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 the amino acids of the peptidoglycan of the cell wall and, thus, the suppression of their synthesis.
The first glycopeptide, vancomycin, was obtained 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 replacement for penicillin in cases of allergy to it in the treatment of infections. However, the rise of drug resistance has become a serious problem. In the 1980s, teicoplanin, an antibiotic from the group of glycopeptides, was obtained. It is prescribed for the same infections, and in combination with gentamicin, it 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 narrow-spectrum antibiotics with a bactericidal effect against gram-positive bacteria, as well as staphylococci resistant to beta-lactam drugs and glycopeptides.
The mechanism of action of antibiotics is significantly different from those already known - in the presence of calcium ions, lipopeptide forms strong bonds with the bacterial cell membrane, which lead to its depolarization and disruption of protein synthesis, as a result of which the harmful cell dies. Firsta member of the lipopeptide class is daptomycin.
daptomycin
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 substances 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 a culture of streptomycetes. During this period, many polyene antibiotics obtained from various fungal cultures - griseofulvin, levorin and others - were included in medical practice. Now fourth-generation polyenes have already been used. They got their common 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 integrated into the cell membrane and forms an ionic wire channel through which the components of the cell pass to the outside, leading to its elimination. Polyenes are fungistatic at low doses and fungicidal at high doses. However, their activity does not extend to bacteria and viruses.
Polymyxins are natural antibiotics produced by soil spore-forming bacteria. In therapy, they found application in the 40s of the last century. These drugs are characterized by bactericidal action, which is caused by damage to the cytoplasmic membrane of the cell of the microorganism, causing its death. Polymyxins are effective against Gram-negative bacteria and are rarely habit-forming. However, too high toxicity limits their use in therapy. Compounds of this group - polymyxin B sulfate and polymyxin M sulfate are rarely used and only as reserve drugs.
Antineoplastic antibiotics
Actinomycins are produced by some radiant fungi and have a cytostatic effect. Natural actinomycins are chromopeptides in structure, differing in amino acids in peptide chains, which determine their biological activity. Actinomycins attract close attention of specialists as antitumor antibiotics. Their mechanism of action is due to the formation of sufficiently stable bonds of the peptide chains of the drug with the double helix of the DNA of the microorganism and the blocking of RNA synthesis as a result.
Dactinomycin, obtained in the 60s of the 20th century, was the first antitumor drug to be used in oncological therapy. However, due to the large number of side effects, this drug is rarely used. More active anticancer drugs have now been obtained.
Anthracyclines are extremely strong antitumor substances isolated from streptomycetes. The mechanism of action of antibiotics is associated with the formation of triple complexes with DNA chains and the breaking of these chains. A second mechanism of antimicrobial action is also possible, due to the production of free radicals that oxidize cancer cells.
Of the 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 forced the search for new compounds that were obtained synthetically. Many of them are successfully used in oncology.
Antibiotics have long entered medical practice and human life. Thanks to them, many diseases were defeated, which for many centuries were considered incurable. Currently, there is such a variety of these compounds that not only the classification of antibiotics according to the mechanism and spectrum of action, but also according to many other characteristics is required.
