Antibiotic-producing microorganisms and their biology

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Antibiotic-producing microorganisms and their biology
Plan.
1. History of antibiotics
2. Antibiotic-producing microorganisms
3. Various antibiotics
Enter.
History of Antibiotics.
The idea of ​​\u1862b\u1868bthe fight against germs belongs to Pasteur, who identified the anthrax bacilli in the pus from 1871-1928. In 10, the Russian doctor visited VA Monassein and AG Polotebkov and told to apply it to infected wounds. But it didn't work out well. Soon, Mechnikov used lactic acid bacteria (lactobacillus) against purulent bacteria in the human intestine. British scientist A. Fleming discovered the first antibiotic, penicillin, in XNUMX. It detects that Penicillium notatum has the ability to lyse a colony of Staphylococcus. But in the last XNUMX years, the study of penicillin has progressed so much that it has been determined that its ability to fight against microbes is low. World War II forced research into antibiotics to treat deep wounds.
In 1940, the British scientists H. Florey and E. Eyen obtained the penicillin drug, which was not purified, contained N.antibiotics, but had high activity. Later, experiments carried out in 39 laboratories in Great Britain and the USA showed that more than 1000 strains of P.notatum and P.chrysogenum were identified, and methods of cultivation and isolation of penicillins and their use in medicine were developed. The structure of penicillin was determined in 1945 using chemical methods and X-ray structural analysis.
(R. Woodward, D. Hodgkin, R. Robinson)
ZA Waxman made a great contribution to the study of antibiotics. He did not isolate the important antibiotics, but developed them using a screening method. Chlorompheninol and tetracycline were discovered in 1948-1950. From 1952 to 1954 and until the 60s, all types of antibiotics were identified. In 1950, 150, in 1960, 1200, and in 1970, more than 2000 antibiotics were identified. Nowadays, the discovery and isolation of antibiotics is much slower. But 50 new substances are discovered per year. Currently, 50 to 100 antibiotics are used in medicine, and 60-65% of them are sold in the world market.
According to the mechanism of action of antibiotics, they can be divided into 4 types
1) inhibitors of bacterial cell wall synthesis
2) m-RNA inhibitor of oxyl synthesis
3) Nucleic acid inhibitor
4) Functionalized cytoplasmic membrane inhibitor.
Antibiotic-producing microorganisms
Many microorganisms have the ability to synthesize various physiologically active substances: enzymes (biological catalysts), vitamins, amino acids, biological stimulants, vaccines and antibiotics. For example, saccharomycete yeasts can synthesize up to 45-50% protein. Some bacteria synthesize antibiotics: thyrothricin, bacitracin, subtilin, polymyxin V. Others synthesize acetic acid. Actinomycetes: various fungi synthesize antibiotics such as streptomycin, aureomycin, neomycin, tetracycline. That is, 2|3 percent of currently known antibiotics are synthesized by actinomycetes.
Mycoplasmas and L-shaped bacteria do not have a cell wall. Often, under the influence of an antibiotic or under natural conditions, L-shaped bacteria can be formed spontaneously. In them, the cell wall is partially preserved, and the reproduction feature is fully preserved. They are large or small spherical and found in many pathogenic and saprophytic bacteria.
It belongs to the order Actinomycetales. They consist of branched hyphae, from which mycelium is formed. Hyphae are unicellular, 0.5-2 µm in diameter. Actinomycetes grown on agar medium contain substrate and aerial mycelia. Air micelles have a straight, spiral appearance. Being spore carriers, spores are used for reproduction. Some actinomycetes have various branched rods instead of aerial micelles. Actinomycetes are saprophytic and pathogenic in humans and animals. Some representatives distinguish antibiotics used in the fight against animal, human and plant diseases.
In microorganisms, there may be one mutation per million cells. For example, resistance to antibiotics, ability to synthesize tryptophan, resistance to phages, changes in the shape of colonies, changes in the formation of pigments or capsular forms becoming non-capsulated, changes in the formation of hivchins, etc. Obtaining new strains of yeasts used in baking, obtaining strains that synthesize large amounts of antibiotics, obtaining strains that synthesize vitamin V12, oils and lipids, obtaining strains that produce lactic acid, or obtaining active prophylactic forms against dysentery, paratyphoid, and typhus, etc. are examples of mutations.
Bacteria, fungi and actinomycetes can be affected by radioactive rays and chemical mutagens, changing the structure of DNA in their cells and directing their activity towards the synthesis of useful substances for humans. Currently, having a good knowledge of the physiological properties of bacteria, changing them and thus using them on a large scale in agricultural, medical, and technological processes is one of the important issues facing microbiologists.
Episomes. Episomes are small clusters of genes that are free from chromosomes. They are found free in the cytoplasm or attached to the bacterial chromosome.
Episomes are involved in the transmission of bacterial virulence (G'), drug resistance (R), bacteriocinogenicity, cholinecinogenicity and other factors. Antibiotic resistance factor (R-factor) of episomes was first identified by Japanese scientists.
Bacteriocinogenicity refers to the property of synthesis of substances against antibiotics in the bacterial cell, these substances are called bacteriocins. For example: Escherichia coli-colicin, Bact. cerlus -aerocin, Bac. synthesizes megaterium-megacin, E. Restis-testicin, Staphylococcus aureus-staphylacoccocin. They are adsorbed to the bacterial cell and cause the death of the bacteria. Bacteriocins affect only bacteria that are close to the producer.
The development of one microorganism with another has been known for centuries. But only in 1942, the term "antibiotic" was introduced into science by ZA Waxman. At present, antibiotics are used as a natural substance in kale and their chemically modified products in low concentration affect the growth of bacteria, fungi, simple viruses and cancer cells, reducing their development.
In the last 40 years, as a result of the use of antibiotics in medicine, various deadly epidemics have been suppressed. For example, cholera. All over the world, infectious diseases (for example, tuberculosis, sepsis, meningitis, pneumonia) do not occur during surgical and birth processes. It is not only developed countries, but developing countries in Central Asia, Africa, and Latin America use antibiotics against these diseases.
The study of the mechanism of antibiotics shows that they affect the function of one or another cellular system, like a thin tool.

Penicillin, cephalosporin and other close antibiotics.
Penicillin affects gram (+) microorganisms (staphylococcus, pneumococcus, streptococcus), some gram (-) organisms (miningococcus, gonococcus), anthrax, clostridium, spirochetes. But sometimes antibiotics can cause allergic diseases and anaphylactic shock.
Penicillin molecule contains  lacto-thiazolidine. The biosynthesis of penicillin takes place according to:
Condensation of L  - aminoadilinic acid leads to the simultaneous change of configuration of L-cysteine ​​and L-valine into a tripeptide. In the next step, isopenicillin N is produced from -lactam. As a result, hydrolysis under the influence of the penicillin acylase enzyme leads to the formation of 6-aminopenicillin acid. In the last fermentation step, phenylacetic acid is converted to penicillin G. Under the influence of phenoxyacetic acid, penicillin turns into V (phenoxymethylpenicillin). Both of these antibiotics have been used for many years.
By the 70s, penicillin lost its importance. Until now, methods of breaking down benzylpenicillin into 6-aminopenicillin acid using enzymatic and chemical methods have been analyzed. Semi-synthetic penicillin was obtained with this method. It is penicillin -lactamase active, resistant and has a wide range of action.
1961 Ye. A. Braham and G. Newton identified a new antibiotic cephalosporin from the extract of the microorganism Cephalosporium acremonium. This antibiotic was not widely used, but cefazolin, cefacetril and cefans were synthesized from it.
In the first half of the 70s, 7-methoxycephalosporin was isolated from the actinomycete streptomyces. 1975 Nocardicin A antibiotic was discovered. In 1981, monobactams, namely sulfazicin, were identified. The mechanism of action of β-lactam antibiotics depends on the bacterial cell wall.

Cycloserine.
This antibiotic was first obtained in 1955 from streptomyces orchidaceus and other actinomycetes. It has a very high antibacterial spectrum and low toxicity to animals, but affects the central nervous system in humans. Therefore, cycloserine is rarely used in the clinic. The structure of cycloserine was analyzed using chemical methods and X-ray structural analysis. 1956 IK Kogekkov, M. Ya. The first synthesis of cycloserine is carried out with the help of Karpeyskin and RM Khomutov. It has now been proven that cycloserine increases the activity of 2 enzymes. These enzymes are involved in the synthesis of D-alanyl-D-alanine synthetase and alanine racemase in the peptidiglycon cell wall.
Tetracycline.
Tetracycline antibiotic is second only to -lactam in its use in medicine. They are used in the fight against gram (+) and often gram (-) bacteria, rickettsia, mycoplasma and pneumonia, dysentery, gonorrhea, cholecystitis, meningitis and infectious diseases.
The first tetracycline antibiotic was isolated from streptomyces aureofaciens in 1948 by B. Daggerom. Later, 6 types of tetracycline were annealed. The structure of the first tetracycline - aureomycin and terramycin was determined in 1952 with the help of a large group of American scientists, including RB Woodwardon using chemical experiments. The main goal of all chemists was to carry out the total synthesis of tetracycline. The first synthesis of tetracycline was carried out in the USSR in 1967 under the leadership of MM Shemyakin and MN Kolosova. Diene condensation of the used substances is used in the formation and then dienediol is used in 6-step modification. Condensation, dehydration, reduction of nitrous ether and mutual protection of amino groups lead mainly to methylation of phenol hydroxide. Tetracycline is formed as a result of hydration of the methylated cycle. The mechanism of action of tetracycline is not yet known. In 1950, it was discovered that tetracycline is a specific inhibitor of oxyl synthesis in Staphylococcus aureus.
Streptomycin and other aminoglycoside antibiotics.
In terms of clinical use, the group of antibiotic deliglycosides occupies the 4th place after -lactam tetracyclines and polyene-free macrolides. Streptomycin, active against gram (-) bacteria, was discovered as a result of the introduction of drugs. It is considered one of the first in the treatment of tuberculosis. Among other aminoglycosides, streptomycin is used against diseases caused by Pseudomonas and Profeus.
Aminoglycosides are a family of many antibiotics and include more than 100 natural compounds. These compounds are derived from microorganisms such as Streptomyces micromonospora and Bacillus as well as many polysynthetic analogues. Their similarity is the presence of 6-membered carbocyclic amino alcohol with glycosylated one and several simple and specific amino saccharides in the molecule structure.
Under the influence of Mg ions, streptomycin binds to the 30 S subunit of the ribosome of prokaryotes and does not affect the ribosome of eukaryotes at all. The purpose of streptomycin is to affect the oxyl ribosome S-12, but the oxyls S-3, S-5, S-7 and S-14 are involved in the binding process. As a result of the interaction of streptomycin with the ribosome, the inhibition of the cleavage of polypeptide bonds begins. In cell-free systems, the genetic code of streptomycin is inducible. But this effect does not depend on its effect on bacteriocytes. At least 2 binding sites have been shown for other aminoglycosides. One of them is the L-6 50 S part of E.coli that holds the oxyl. Xamda calls the error calculation property.
Conclusion
Many microorganisms have the ability to synthesize various physiologically active substances: enzymes (biological catalysts), vitamins, amino acids, biological stimulants, vaccines and antibiotics.
Actinomycetes: various fungi synthesize antibiotics such as streptomycin, aureomycin, neomycin, tetracycline. That is, 2|3 percent of currently known antibiotics are synthesized by actinomycetes. It has a very high antibacterial spectrum and low toxicity to animals, but affects the central nervous system in humans.
Books
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2. Schlegel G. Obshaya microbiology. M., 1987.
3. Gusev MV, Mineyeva LA, Microbiology. M. Izd-vo MGU, 1985
4. Agol VI, Atabekov IG, Tikhonenko TI, Krylov VN Molekularnaya biologiya virusov. M. Nauka, 1971.
5. Vahobov AH, Inoghomov M. Microbiology (Lecture text). Tashkent. ToshDU publishing house. 1999
6. Vahobov AH, Inoghomov M. Fundamentals of microbiology and virology. "Teacher", 1999.
7. Inoghomov M. Fundamentals of microbiology and virology. "Teacher", 1983.

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