Penicillin: How Fleming's Discovery Became an Antibiotic. Genus Penicillium (Penicillium) Penicillin is used for pneumonia, sepsis, pustular skin diseases, tonsillitis, scarlet fever, diphtheria, rheumatism, syphilis, gonorrhea and other diseases caused by

03.05.2020

“When I woke up at dawn on September 28, 1928, I certainly did not plan a revolution in medicine with my discovery of the world’s first antibiotic or killer bacteria,” this diary entry was made by Alexander Fleming the man who invented penicillin.

The idea of using microbes to fight germs dates back to the 19th century. It was already clear to scientists then that in order to deal with wound complications, one must learn to paralyze the microbes that cause these complications, and that microorganisms can be killed with their own help. In particular, Louis Pasteur discovered that anthrax bacilli are killed by some other microbes. In 1897 Ernest Duchesne used the mold, that is, the properties of penicillin, to treat typhus in guinea pigs.

In fact, the date of the invention of the first antibiotic is September 3, 1928. By this time, Fleming was already known and had a reputation as a brilliant researcher, he was studying staphylococci, but his laboratory was often untidy, which was the reason for the discovery.

Penicillin. Photo: www.globallookpress.com

On September 3, 1928, Fleming returned to his laboratory after a month's absence. Having collected all the cultures of staphylococci, the scientist noticed that mold fungi appeared on one plate with the cultures, and the colonies of staphylococci present there were destroyed, while other colonies were not. Fleming attributed the fungi that grew on the plate with his cultures to the genus Penicillaceae, and called the isolated substance penicillin.

In the course of further research, Fleming noticed that penicillin affects bacteria such as staphylococci and many other pathogens that cause scarlet fever, pneumonia, meningitis and diphtheria. However, the remedy allocated by him did not help against typhoid and paratyphoid fever.

Continuing his research, Fleming found that penicillin was difficult to work with, production was slow, and penicillin could not exist in the human body long enough to kill bacteria. Also, the scientist could not extract and purify the active substance.

Until 1942, Fleming improved the new drug, but until 1939 it was not possible to develop an effective culture. In 1940 the German-English biochemist Ernst Boris Chain and Howard Walter Florey, an English pathologist and bacteriologist, were actively engaged in an attempt to purify and isolate penicillin, and after a while they managed to produce enough penicillin to treat the wounded.

In 1941, the drug was accumulated in sufficient quantities for an effective dose. The first person to be saved with the new antibiotic was a 15-year-old teenager with blood poisoning.

In 1945, Fleming, Flory and Chain were awarded the Nobel Prize in Physiology or Medicine "for their discovery of penicillin and its curative effects in various infectious diseases."

The value of penicillin in medicine

At the height of World War II in the United States, the production of penicillin was already put on the conveyor, which saved tens of thousands of American and allied soldiers from gangrene and amputation of limbs. Over time, the antibiotic production method was improved, and since 1952, the relatively cheap penicillin began to be used on an almost global scale.

With the help of penicillin, osteomyelitis and pneumonia, syphilis and puerperal fever can be cured, infections can be prevented after injuries and burns - before all these diseases were fatal. In the course of the development of pharmacology, antibacterial drugs of other groups were isolated and synthesized, and when other types of antibiotics were obtained,.

drug resistance

For several decades, antibiotics have become almost a panacea for all diseases, but the discoverer Alexander Fleming himself warned that penicillin should not be used until the disease is diagnosed, and the antibiotic should not be used for a short time and in very small quantities, since under these conditions bacteria develop resistance.

When pneumococcus, not sensitive to penicillin, was identified in 1967, and antibiotic-resistant strains of Staphylococcus aureus were discovered in 1948, it became clear to scientists that.

“The discovery of antibiotics was the greatest boon for mankind, the salvation of millions of people. Man created more and more antibiotics against various infectious agents. But the microcosm resists, mutates, microbes adapt. A paradox arises - people develop new antibiotics, and the microcosm develops its own resistance, ”said Galina Kholmogorova, senior researcher at the State Research Center for Preventive Medicine, Candidate of Medical Sciences, expert of the League of Nation's Health.

According to many experts, the fact that antibiotics lose their effectiveness in fighting diseases is largely to blame for the patients themselves, who do not always take antibiotics strictly according to indications or in the required doses.

“The problem of resistance is exceptionally large and affects everyone. It causes great concern to scientists, we can return to the pre-antibiotic era, because all microbes will become resistant, not a single antibiotic will work on them. Our inept actions have led to the fact that we may be without very powerful drugs. There will simply be nothing to treat such terrible diseases as tuberculosis, HIV, AIDS, malaria,” explained Galina Kholmogorova.

That is why antibiotic treatment should be treated very responsibly and follow a number of simple rules, in particular:

Penicilli rightfully occupy the first place in distribution among hyphomycetes. Their natural reservoir is the soil, and, being cosmopolitan in most species, unlike aspergillus, they are confined more to the soils of northern latitudes.

Like Aspergillus, they are most often found as molds, consisting mainly of conidiophores with conidia, on a wide variety of substrates, mainly of plant origin.

Representatives of this genus were discovered simultaneously with Aspergillus due to their generally similar ecology, wide distribution and morphological similarity.

The mycelium of penicillium in general does not differ from the mycelium of aspergillus. It is colorless, multicellular, branching. The main difference between these two closely related genera lies in the structure of the conidial apparatus. In penicilli, it is more diverse and is in the upper part a brush of varying degrees of complexity (hence its synonym "brush"). Based on the structure of the brush and some other characters (morphological and cultural), sections, subsections and series are established within the genus.

The simplest conidiophores in penicilli bear only a bundle of phialides at the upper end, forming chains of conidia developing basipetally, as in aspergillus. Such conidiophores are called monomerous or monoverticillate (section Monoverticillata, Fig. 231). A more complex brush consists of metulae, i.e., more or less long cells located at the top of the conidiophore, and on each of them there is a bundle, or whorl, of phialides. In this case, the metulae can be either in the form of a symmetrical bundle (Fig. 231), or in a small number, and then one of them, as it were, continues the main axis of the conidiophore, while the others are not symmetrically located on it (Fig. 231). In the first case, they are called symmetrical (section Biverticillata-symmetrica), in the second - asymmetric (section Aeumetrica). Asymmetric conidiophores can have an even more complex structure: the metulae then depart from the so-called branches (Fig. 231). And finally, in a few species, both twigs and metulae can be located not in one "floor", but in two, three or more. Then the brush turns out to be multi-storey, or multi-whorled (section Polyverticillata). In some species, conidiophores are combined into bundles - coremia, especially well developed in the subsection Asymmetrica-Fasciculata. When the coremia are predominant in a colony, they can be seen with the naked eye. Sometimes they are 1 cm high or more. If coremia is weakly expressed in a colony, then it has a powdery or granular surface, most often in the marginal zone.

Details of the structure of conidiophores (they are smooth or spiny, colorless or colored), the size of their parts can be different in different series and in different species, as well as the shape, structure of the shell and the size of mature conidia (Table 56).

As well as in Aspergillus, some penicilli have a higher sporulation - marsupial (sexual). Asci also develop in leistothecia, similar to Aspergillus cleistothecia. These fruiting bodies were first depicted in the work of O. Brefeld (1874).

It is interesting that in penicilli there is the same pattern that was noted for aspergillus, namely: the simpler the structure of the conidiophorous apparatus (tassels), the more species we find cleistothecia. Thus, they are most often found in sections Monoverticillata and Biverticillata-Symmetrica. The more complex the brush, the fewer species with cleistothecia occur in this group. Thus, in the subsection Asymmetrica-Fasciculata, which is characterized by particularly powerful conidiophores united in coremia, there is not a single species with cleitothecia. From this we can conclude that the evolution of penicilli went in the direction of the complication of the conidial apparatus, the increasing production of conidia and the extinction of sexual reproduction. On this occasion, some considerations can be made. Since penicilli, like aspergilli, have heterokaryosis and a parasexual cycle, these features represent the basis on which new forms can arise that adapt to different environmental conditions and are able to conquer new living spaces for individuals of the species and ensure its prosperity. . In combination with the huge number of conidia that arise on the complex conidiophore (it is measured in tens of thousands), while the number of spores in the asci and in the leistothecia as a whole is incommensurably smaller, the total production of these new forms can be very high. Thus, the presence of a parasexual cycle and efficient formation of conidia, in essence, provides fungi with the benefit that the sexual process delivers to other organisms compared to asexual or vegetative reproduction.

In the colonies of many penicilli, as in Aspergillus, there are sclerotia, which apparently serve to endure unfavorable conditions.

Thus, the morphology, ontogeny, and other features of Aspergillus and Penicilli have much in common, which suggests their phylogenetic closeness. Some penicilli from the section Monoverticillata have a strongly dilated apex of the conidiophore, resembling the swelling of the Aspergillus conidiophore, and, like Aspergillus, are more common in southern latitudes. Therefore, one can imagine the relationship between these two genera and the evolution within these genera as follows:

Attention to penicilli increased when they were first discovered to form the antibiotic penicillin. Then scientists of various specialties joined the study of penicillins: bacteriologists, pharmacologists, physicians, chemists, etc. This is quite understandable, since the discovery of penicillin was one of the outstanding events not only in biology, but also in a number of other areas, especially in medicine , veterinary medicine, phytopathology, where antibiotics then found the widest application. Penicillin was the first antibiotic discovered. The widespread recognition and use of penicillin played a big role in science, as it accelerated the discovery and introduction of other antibiotic substances into medical practice.

The medicinal properties of molds formed by penicillium colonies were first noted by Russian scientists V. A. Manassein and A. G. Polotebnov back in the 70s of the last century. They used these molds to treat skin diseases and syphilis.

In 1928 in England, Professor A. Fleming drew attention to one of the cups with a nutrient medium, on which the bacterium staphylococcus was sown. A colony of bacteria stopped growing under the influence of blue-green mold that got from the air and developed in the same cup. Fleming isolated the fungus in pure culture (which turned out to be Penicillium notatum) and demonstrated its ability to produce a bacteriostatic substance, which he named penicillin. Fleming recommended the use of this substance and noted that it could be used in medicine. However, the significance of penicillin became fully apparent only in 1941. Flory, Cheyne and others described the methods for obtaining, purifying penicillin and the results of the first clinical trials of this drug. After that, a program of further research was outlined, including the search for more suitable media and methods for cultivating fungi and obtaining more productive strains. It can be considered that the history of scientific selection of microorganisms began with the work on increasing the productivity of penicilli.

Back in 1942-1943. it was found that the ability to produce a large amount of penicillin also have some strains of another species - P. chrysogenum (Table 57). Active strains were isolated in the USSR in 1942 by Professor 3. V. Ermolyeva and co-workers. Many productive strains have also been isolated abroad.

Initially, penicillin was obtained using strains isolated from various natural sources. These were strains of P. notaturn and P. chrysogenum. Then, isolates were selected that gave a higher yield of penicillin, first under surface and then immersed culture in special fermenter vats. A mutant Q-176 was obtained, which is characterized by even higher productivity, which was used for the industrial production of penicillin. In the future, on the basis of this strain, even more active variants were selected. Work on obtaining active strains is ongoing. Highly productive strains are obtained mainly with the help of potent factors (X-ray and ultraviolet rays, chemical mutagens).

The medicinal properties of penicillin are very diverse. It acts on pyogenic cocci, gonococci, anaerobic bacteria that cause gas gangrene, in cases of various abscesses, carbuncles, wound infections, osteomyelitis, meningitis, peritonitis, endocarditis and makes it possible to save the life of patients when other medical drugs (in particular, sulfa drugs) are powerless .

In 1946, it was possible to carry out the synthesis of penicillin, which was identical to the natural, obtained biologically. However, the modern penicillin industry is based on biosynthesis, since it makes it possible to mass-produce a cheap drug.

Of the section Monoverticillata, whose representatives are more common in more southern regions, the most common is Penicillium frequentans. It forms widely growing velvety green colonies with a reddish-brown underside on a nutrient medium. Chains of conidia on one conidiophore are usually connected in long columns, clearly visible at low magnification of the microscope. P. frequentans produces the enzymes pectinase, which is used to clear fruit juices, and proteinase. At low acidity of the medium, this fungus, like P. spinulosum, close to it, forms gluconic acid, and at higher acidity, citric acid.

P. thomii is usually isolated from forest soils and litter of mainly coniferous forests in different parts of the world (Tables 56, 57), easily distinguished from other penicilli of the section Monoverticillata by the presence of pink sclerotia. Strains of this species are highly active in the destruction of tannin, and they also form penicillic acid, an antibiotic that acts on gram-positive and gram-negative bacteria, mycobacteria, actinomycetes, and some plants and animals.

Many species from the same section Monoverticillata were isolated from items of military equipment, from optical instruments and other materials in subtropical and tropic conditions.

Since 1940, in Asian countries, especially in Japan and China, a serious disease of people called poisoning from yellow rice has been known. It is characterized by severe damage to the central nervous system, motor nerves, disorders of the cardiovascular system and respiratory organs. The cause of the disease was the fungus P. citreo-viride, which secretes the toxin citreoviridin. In this regard, it was suggested that when people get beriberi, along with beriberi, acute mycotoxicosis also occurs.

Representatives of the Biverticillata-symmetrica section are of no less importance. They are isolated from various soils, from plant substrates and industrial products in the subtropics and tropics.

Many of the fungi in this section are distinguished by the bright color of the colonies and secrete pigments that diffuse into the environment and color it. With the development of these fungi on paper and paper products, on books, art objects, awnings, car upholstery, colored spots form. One of the main mushrooms on paper and books is P. purpurogenum. Its wide-growing velvety yellowish-green colonies are framed by a yellow border of growing mycelium, and the reverse side of the colony has a purple-red color. The red pigment is also released into the environment.

Particularly widespread and important among penicilli are representatives of the section Asymmetrica.

We have already mentioned the producers of penicillin - P. chrysogenum and P. notatum. They are found in soil and on various organic substrates. Macroscopically, their colonies are similar. They are green in color, and, like all species of the P. chrysogenum series, they are characterized by the release of yellow exudate and the same pigment into the medium on the surface of the colony (Table 57).

It can be added that both of these species, together with penicillin, often form ergosterol.

The penicilli from the P. roqueforti series are of great importance. They live in the soil, but predominate in the group of cheeses characterized by "marbling". This is Roquefort cheese, which is native to France; cheese "Gorgonzola" from Northern Italy, cheese "Stiltosh" from England, etc. All these cheeses are characterized by a loose structure, a specific appearance (streaks and spots of bluish-green color) and a characteristic aroma. The fact is that the corresponding cultures of mushrooms are used at a certain point in the process of making cheeses. P. roqueforti and related species are able to grow in loosely pressed cottage cheese because they tolerate a low oxygen content well (in the mixture of gases formed in the voids of the cheese, it contains less than 5%). In addition, they are resistant to high salt concentration in an acidic environment and form lipolytic and proteolytic enzymes that act on the fat and protein components of milk. Currently, selected strains of fungi are used in the process of making these cheeses.

From soft French cheeses - Camembert, Brie, etc. - P. camamberti and R. caseicolum were isolated. Both of these species have so long and so adapted to their specific substrate that they are almost not distinguished from other sources. At the final stage of the production of Camembert or Brie cheeses, the curd mass is placed for maturation in a special chamber with a temperature of 13-14 ° C and a humidity of 55-60%, the air of which contains spores of the corresponding fungi. Within a week, the entire surface of the cheese is covered with a fluffy white coating of mold 1-2 mm thick. Within about ten days, the mold coating becomes bluish or greenish-gray in the case of P. camamberti, or remains white with the predominant development of P. caseicolum. The mass of cheese under the influence of fungal enzymes acquires juiciness, oiliness, specific taste and aroma.

P. digitatum releases ethylene, which causes faster ripening of healthy citrus fruits in the vicinity of fruits affected by this fungus.

P. italicum is a blue-green mold that causes soft rot in citrus fruits. This fungus affects oranges and grapefruits more often than lemons, while P. digitatum develops with equal success on lemons, oranges and grapefruits. With the intensive development of P. italicum, the fruits quickly lose their shape and become covered with slime spots.

Conidiophores of P. italicum often coalesce in coremia, and then the mold coating becomes granular. Both mushrooms have a pleasant aromatic smell.

In the soil and on various substrates (grain, bread, manufactured goods, etc.), P. expansum is often found (Table 58). But it is especially known as the cause of the rapidly developing soft brown rot of apples. The loss of apples from this fungus during storage is sometimes 85-90%. Conidiophores of this species also form coremia. Masses of its spores present in the air can cause allergic diseases.

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penicillin, penicillin series
Penicillium Link, 1809

(lat. Penicillium) - a fungus that forms on food and, as a result, spoils them. Penicillium notatum, one of the species of this genus, is the source of the first ever antibiotic penicillin, invented by Alexander Fleming.

1 Opening penicillium
2 Reproduction and structure of the penicillium
3 Origin of the term
4 See also
5 Links

Opening penicillium

In 1897, a young military doctor from Lyon named Ernest Duchene made a "discovery" by observing how Arab groom boys used mold from still damp saddles to treat wounds on the backs of horses rubbed with these same saddles. Duchene carefully examined the taken mold, identified it as Penicillium glaucum, tested it on guinea pigs for the treatment of typhus and found its destructive effect on Escherichia coli bacteria. It was the first ever clinical trial of what would soon become world famous penicillin.

The young man presented the results of his research in the form of a doctoral dissertation, persistently offering to continue work in this area, but the Pasteur Institute in Paris did not even bother to confirm receipt of the document - apparently because Duchenne was only twenty-three years old.

Well-deserved fame came to Duchenne after his death, in 1949 - 4 years after Sir Alexander Flemming was awarded the Nobel Prize for the discovery (for the third time) of the antibiotic effect of penicillium.

Reproduction and structure of the penicillium

The natural habitat of the penicillium is the soil. Penicillium can often be seen as a green or blue moldy coating on a variety of substrates, mostly vegetable. The fungus penicillium has a similar structure to aspergillus, also related to mold fungi. The vegetative mycelium of the penicilla is branching, transparent and consists of many cells. The difference between penicillium and mucor is that its mycelium is multicellular, while that of mucor is unicellular. The hyphae of the fungus penicilla are either immersed in the substrate or located on its surface. Erect or ascending conidiophores depart from the hyphae. These formations branch in the upper section and form brushes carrying chains of unicellular colored spores - conidia. Penicillium brushes can be of several types: single-tier, two-tier, three-tier and asymmetrical. In some species of penicilla, conidium conidia form bundles - coremia. Reproduction of penicillium occurs with the help of spores.

Origin of the term

The term penicillium was coined by Flemming in 1929. By a lucky coincidence, which was the result of a combination of circumstances, the scientist drew attention to the antibacterial properties of the mold, which he identified as Penicillium rubrum. As it turned out, Flemming's definition was wrong. Only many years later, Charles Tom corrected his assessment and gave the fungus the correct name - Penicillum notatum.

This mold was originally called Penicillium due to the fact that under a microscope its spore-bearing legs looked like tiny brushes.

Links

penicillamine, penicillin, penicillin gezh yu ve, penicillin instruction, penicillin history, penicillin discovery, penicillin formula, penicillin series, 5th generation penicillins, penicillins bulgiin

Penicill Information About

Molds found in temperate climates have not yet been considered as independent causative agents of onychomycosis - a fungal disease of the nails. It was believed that these fungi are not able to destroy the keratin of the nail plate.

However, thanks to the new possibilities of medical technology, it has been shown that mold fungi contain enzymes that break down keratin, and the ability of these microorganisms to independently cause onychomycosis has been proven.

Molds are especially dangerous for people with weakened immune systems. Molds can infect the skin, nails, penetrate the lungs with air, causing fungal diseases of the internal organs.

Mold onychomycosis is caused mainly by fungi from the genera:

Mold fungi Aspergillus are capable of destroying the keratin of the nail and causing onychomycosis on their own,Scopulariopsis (S.brevicaulis),Scytalidium,Fusarium,Acremonium.

The nails on the big toes of the elderly are predominantly affected.

We draw your attention to the fact that not only mold fungi cause onychomycosis. We suggest that you read our next article about other types of onychomycosis and its pathogens.

Features of the treatment of mold onychomycosis

The drugs of choice in the treatment of mold fungi on the nails are antifungals with itraconazole Irunin, Orungal. These antimycotics have a wide spectrum of action, are effective against dermatophytes, Candida yeast-like fungi, mold fungi.

Itraconazole in the treatment of nail mold is more often prescribed according to the pulse therapy regimen: 400 mg daily for a week, then a break for 3 weeks.

An interval of 1 week of admission / 3 weeks of rest corresponds to one pulse. In the course of treatment, there may be several such pulses, depending on the aggressiveness of the fungus and the state of health of the patient.

The duration of treatment, depending on the type of mold, is from 3 to 12 months.

Also used terbinafine (Lamisil), ketoconazole. Treatment for mold on the nails with antifungal drugs in tablets is combined with local application of varnish with ciclopirox (Batrafen, fungal), removing the nail plate if necessary.

The symptoms of onychomycosis mold are sometimes difficult to distinguish from dermatophyte nail fungus.

The similarity of toenail fungus caused by molds and dermatophytes can lead to errors in the choice of treatment, which makes traditional treatments for onychomycosis ineffective.

Nail fungus caused by Aspergillus

Onychomycosis is caused by several types of Aspergillus fungi, including Aspergillus niger, which gives black staining of the crescent (base, matrix) of the nail.

More often, aspergillus causes distal and superficial onychomycosis, manifested by a thickened white nail, pain in the nail folds.

Scheme mold fungus treatment Aspergillus on toenails consists in taking 500 mg every day for a week terbinafine followed by a rest period of 3 weeks.

Treatment of onychomycosis in Fusarium infection

Molds of the genus Fusarium cause onychomycosis when the nail is injured, through wounds on the skin. There is a fungus in the soil, on plants. Fusarium causes diseases (fusarium wilt) of tomatoes, pears, cereals.

Not only people working with the earth are at risk of contracting mold onychomycosis. At high humidity, the fungus is found in house dust, mattresses, upholstered furniture, and ventilation systems.

Fusarium causes nail fungus on the feet and hands. When penetrating through the lungs with air, it can affect blood vessels, provoking thrombosis, heart attacks.

Fusarium onychomycosis is difficult to treat. The fungus is sensitive to voriconazole, itraconazole in combination with terbinafine.

As a systemic treatment, the patient is prescribed pulse therapy. Irunin at a dosage of 400-600 mg per day, and topically apply varnish with ciclopirox.

Nail fungus Scopulariopsis brevicaulis

More often than other molds, onychomycosis in temperate climates is caused by Scopulariopsis brevicaulis. Scopulariopsis mushrooms settle under wallpaper, in carpets, mattresses.

Mold is extremely common in temperate climates, found in swimming pools, on food, in soil, and on bookshelves. A symptom of infection is white, like chalk, the color of the nail.

The fungus occurs on the toenails, more often after an injury at the base of the nail plate, treatment is complex with local antifungal ointments and itraconazole / terbinafine.

Treatment of nail fungus Scytalidium dimidiatum

The natural source of distribution of this mold fungus is citrus and mango plantations in the tropics. Diabetes mellitus is a predisposing factor.

The appearance of Scytalidium dimidiatum in European countries is associated with population migration. This fungus causes diseases of the skin, nails of the feet, hands, is the cause of mycetoma, fungemia - fungal sepsis.

Primarily, the fungus appears on the toenails, then spreads to the skin of the feet, and without treatment, it passes into the blood, into deep tissues.

Against the mold Scytalidium dimidiatum is used amphotericin B, topical antifungals, new systemic antimycotics voriconazole, posaconazole.

You may be interested in an article about folk methods of treating nail fungus.

Onychomycosis due to Alternaria fungus infection

Mold onychomycosis caused by Alternaria is expressed in dystrophic changes in the nail plate, hyperkeratosis of the big toe and the second toe adjacent to it. Fingernails are rarely affected.

The drugs of choice for the treatment of toenail fungus caused by molds of the genus Alternaria are itraconazole (Irunin) and amphotericin B. Treatment lasts from 3 to 6 months, Irunin is taken at a dose of 200-400 mg per day, amphotericin B is prescribed at the rate of 0.3 mg or 0.5 mg per 1 kg of body weight per day.

Forecast

Compliance with preventive measures against the colonization of the human habitat with mold fungi, timely contact with a mycologist reduces the risk of infection.

Systematic position

Superkingdom - eukaryotes, kingdom - fungi
Family Mucinaceae. Class imperfect mushrooms.
Among the mushrooms widely distributed in nature, the most important for medicinal purposes are green racemose molds belonging to the genus of penicillium Penicillium, many species of which are capable of forming penicillin. For the production of penicillin, penicillin golden is used. This is a microscopic mushroom with a cloisonne branched mycelium that makes up the mycelium.

Morphology.
Mushrooms are eukaryotes and belong to anhydrous lower plants. They differ both in their more complex structure and in more advanced methods of reproduction.
As already mentioned, fungi are represented by both unicellular and multicellular microorganisms. Unicellular fungi include yeast and yeast-like cells of irregular shape, much larger than bacteria. Multicellular fungi-microorganisms are molds, or micellar fungi.
The body of a multicellular fungus is called thal, or mycelium. The basis of the mycelium is hypha - a multinucleated filamentous cell. Mycelium can be septate (hyphae are separated by partitions and have a common shell). Tissue forms of yeast can be represented by pseudomycelium, its formation is the result of budding of unicellular fungi without the discharge of daughter cells. Pseudomycelium, unlike the true one, does not have a common shell.
The mycelium of penicillium in general does not differ from the mycelium of aspergillus. It is colorless, multicellular, branching. The main difference between these two closely related genera lies in the structure of the conidial apparatus. In penicilli, it is more diverse and is in the upper part a brush of varying degrees of complexity (hence its synonym "brush"). Based on the structure of the brush and some other features (morphological and cultural), sections, subsections and series were established within the genus (Fig. 1)

Rice. 1 Sections, subsections and series.

The simplest conidiophores in penicilli bear only a bundle of phialides at the upper end, forming chains of conidia developing basipetally, as in aspergillus. Such conidiophores are called monoverticillate or monoverticillate (section Monoverticillata,. A more complex brush consists of metulae, i.e., more or less long cells located on the top of the conidiophore, and on each of them there is a bundle, or whorl, phialides. At the same time, metula can be either in the form of a symmetrical bundle or in a small amount, and then one of them, as it were, continues the main axis of the conidiophore, while the others are not symmetrically located on it. Aeumetrica). Asymmetric conidiophores can have an even more complex structure: the metulae then depart from the so-called branches. And finally, in a few species, both branches and metulae can be located not in one "floor", but in two, three or more. Then the brush turns out to be multi-storey, or multi-whorled (section Polyverticillata).In some species, conidiophores are combined into bundles - coremia, especially x well developed in subsection Asymmetrica-Fasciculata. When the coremia are predominant in a colony, they can be seen with the naked eye. Sometimes they are 1 cm high or more. If coremia is weakly expressed in a colony, then it has a powdery or granular surface, most often in the marginal zone.

Details of the structure of conidiophores (they are smooth or spiny, colorless or colored), the sizes of their parts can be different in different series and in different species, as well as the shape, structure of the shell and the size of mature conidia (Fig. 2)

Rice. 2 shape, shell structure and size of mature conidia.

The structural basis of penicillins is 6-aminopenicillanic acid. When the b-lactam ring is cleaved by bacterial b-lactamases, inactive penicillanic acid is formed, which does not have antibacterial properties. Differences in the biological properties of penicillins determine the radicals at the amino group of 6-aminopenicillanic acid.
. Absorption of antibiotics by microbial cells.
The first stage in the interaction of microorganisms with antibiotics is its adsorption by cells. Pasynsky and Kostorskaya (1947) established for the first time that one cell of Staphylococcus aureus absorbs approximately 1,000 penicillin molecules. In subsequent studies, these calculations were confirmed.
So, according to Maas and Johnson (1949), approximately 2 (10-9 M penicillin) is absorbed by 1 ml of staphylococci, and about 750 molecules of this antibiotic are irreversibly bound by one microorganism cell without a visible effect on its growth.
Eagle et al (1955) determined that when 1,200 molecules of penicillin are bound by a bacterial cell, inhibition of bacterial growth is not observed.
Inhibition of the growth of a microorganism by 90% is observed in cases where from 1,500 to 1,700 molecules of penicillin are bound to the cell, and when up to 2,400 molecules per cell are absorbed, the culture rapidly dies.
It has been established that the process of adsorption of penicillin does not depend on the concentration of the antibiotic in the medium. At low drug concentrations
(about 0.03 μg/ml) it can be completely adsorbed by cells, and further increase in the concentration of the substance will not lead to an increase in the amount of bound antibiotic.
There is evidence (Cooper, 1954) that phenol prevents the absorption of penicillin by bacterial cells, but it does not have the ability to free cells from the antibiotic.
Penicillin, streptomycin, gramicidin C, erythrin and other antibiotics are bound by various bacteria in appreciable amounts. Moreover, polypeptide antibiotics are adsorbed by microbial cells to a greater extent than, for example, penicillins and streptomycin.

Rice. 3. The structure of penicillins: 63 - benzylpenicillin (G); 64 - n-oxybenzylpenicillin (X); 65 - 2-pentenylpenicillin (F); 66 - p-amylpenicillin (dihydro F)6; 67 -P-heptylpenicillin (K); 68 - phenoxymethylpenicillin (V); 69 - allylmercaptomethylpenicillin (O); 70 - ?-phenoxyethylpenicillin (pheneticillin); 71 - ?-phenoxypropylpenicillin (propicillin); 72 - ?-phenoxybenzylpenicillin (fenbenicillin); 73 - 2,6-dimethoxyphenylpenicillin (methicillin); 74 - 5-methyl-3-phenyl-4-isooxyazolylpenicillin (oxacillin); 75 - 2-ethoxy-1-naphthylpenicillin (nafcillin); 76 - 2-biphenylylpenicillin (difenicillin); 77 - 3-O-chlorophenyl-5-methyl-4-isooxazolyl (cloxacillin); 78 -?-D-(-)-aminobenzylpenicillin (ampicillin).
Penicillins are associated with the formation of so-called L-forms in bacteria; cm.Shapes of bacteria . ) Some microbes (for example, staphylococci) form the enzyme penicillinase, which inactivates penicillins by breaking the b-lactam ring. The number of such microbes resistant to the action of Penicillins is increasing due to the widespread use of Penicillins (for example, about 80% of strains of pathogenic staphylococci isolated from patients are resistant to PD).

After separation in 1959 from. chrysogenum 6-APK, it became possible to synthesize new penicillins by adding various radicals to the free amino group. More than 15,000 semi-synthetic Penicillins (PSP) are known, but only a few of them surpass PP in biological properties. Some PSPs (methicillin, oxacillin, etc.) are not destroyed by penicillinase and therefore act on PD-resistant staphylococci, others are stable in an acidic environment and therefore, unlike most PPs, can be used orally (pheneticillin, propicillin). There are PSPs with a broader spectrum of antimicrobial action than those of BP (ampicillin, carbenicillin). Ampicillin and oxacillin, in addition, are acid-resistant and well absorbed in the gastrointestinal tract. All Penicillins have low toxicity, however, in some patients with hypersensitivity to Penicillins, they can cause side effects - allergic reactions (urticaria, swelling of the face, joint pain, etc.).
Penicilli rightfully occupy the first place in distribution among hyphomycetes. Their natural reservoir is the soil, and, being cosmopolitan in most species, unlike aspergillus, they are confined more to the soils of northern latitudes.

Life features.
Reproduction.
cultivation conditions. As the only source of carbon in the medium, lactose is recognized as the best compound for the biosynthesis of penicillin, since it is utilized by the fungus more slowly than, for example, glucose, as a result of which lactose is still contained in the medium during the period of maximum formation of the antibiotic. Lactose can be replaced by easily digestible carbohydrates (glucose, sucrose, galactose, xylose) provided that they are continuously introduced into the medium. With the continuous introduction of glucose into the medium (0.032 wt.% / h), the yield of penicillin on the corn medium increases by 15% compared to the use of lactose, and on the synthetic medium - by 65%.
Some organic compounds (ethanol, unsaturated fatty acids, lactic and citric acids) enhance the biosynthesis of penicillin.
Sulfur plays an important role in the process of biosynthesis. Antibiotic producers use sulfates and thiosulfates well as sulfur.
As a source of phosphorus P. chrysogenum can use both phosphates and phytates (salts of inositol phosphoric acids).
Of great importance for the formation of penicillin is the aeration of the culture; its maximum accumulation occurs at aeration intensity close to unity. Reducing the intensity of aeration or its excessive increase reduces the yield of the antibiotic. Increasing the intensity of mixing also contributes to the acceleration of biosynthesis.
Thus, a high yield of penicillin is obtained under the following conditions for the development of the fungus; good growth of mycelium, sufficient provision of culture with nutrients and oxygen, optimal temperature (during the first phase 30 °C, during the second phase 20 °C), pH level = 7.0–8.0, slow consumption of carbohydrates, suitable precursor.
For the industrial production of an antibiotic, a medium of the following composition is used, %: corn extract (CB) - 0.3; hydrol - 0.5; lactose - 0.3; NH 4 NO 3 - 0.125; Na2SO3? 5H 2 O - 0.1; Na2SO4? 10H 2 O - 0.05; MgSO4? 7H 2 O - 0.025; MnSO 4 ? 5H 2 O - 0.002; ZnSO 4 - 0.02; KH 2 PO 4 - 0.2; CaCO 3 - 0.3; phenylacetic acid - 0.1.
Quite often, sucrose or a mixture of lactose and glucose in a ratio of 1: 1 is used. In some cases, instead of corn extract, peanut flour, oilcake, cottonseed flour and other plant materials are used.

Breath.
According to the type of respiration in the environment, fungi are aerobes, their tissue forms (when they enter the macroorganism) are facultative anaerobes.
Breathing is accompanied by a significant release of heat. Heat is especially energetically released during the respiration of fungi and bacteria. The use of manure in greenhouses as a biofuel is based on this property. In some plants, during respiration, the temperature rises by several degrees relative to the ambient temperature.
Most bacteria use free oxygen in the process of respiration. Such microorganisms are called aerobic (from aer - air). Aerobic s and the type of respiration is characterized by the fact that the oxidation of organic compounds occurs with the participation of atmospheric oxygen with the release of a large number of calories. Molecular oxygen plays the role of an acceptor of hydrogen formed during the aerobic splitting of these compounds.
An example is the oxidation of glucose under aerobic conditions, which leads to the release of a large amount of energy:
SvH12Ov + 602- * 6C02 + 6H20 + 688.5 kcal.
The process of anaerobic respiration of microbes is that bacteria obtain energy from redox reactions, in which the hydrogen acceptor is not oxygen, but inorganic compounds - nitrate or sulfate.

Ecology of microorganisms.
The action of environmental factors.
Microorganisms are constantly exposed to environmental factors. Adverse effects can lead to the death of microorganisms, that is, to have a microbicidal effect, or to suppress the reproduction of microbes, providing a static effect. Some impacts have a selective effect on certain species, others show a wide range of activity. Based on this, methods have been created to suppress the vital activity of microbes, which are used in medicine, everyday life, agriculture, etc.
Temperature
In relation to temperature conditions, microorganisms are divided into thermophilic, psychrophilic and mesophilic. Penicillin is also produced by the thermophilic organism Malbranchia pulchella.
The development of molds depends on the availability of readily available sources of nitrogen and carbon nutrition, while xylotrophic fungi are capable of destroying complex hard-to-reach lignocellulosic straw complexes. Treatment of the substrate at high temperature causes hydrolysis of plant polysaccharides and the appearance of free easily digestible sugars, which contribute to the reproduction of competitive molds. A selective substrate that inhibits the development of molds and favors the growth of mycelium is obtained by processing at a moderate temperature of 65 - 70 ° C. Increasing the processing temperature to 75 - 85 ° leads to the stimulation of mold development
Humidity
When the relative humidity of the environment is below 30%, the vital activity of most bacteria stops. The time of their death during drying is different (for example, Vibrio cholerae - in 2 days, and mycobacteria - in 90 days). Therefore, drying is not used as a method of eliminating microbes from substrates. Bacterial spores are particularly resistant.
Artificial drying of microorganisms is widespread, or lyophilization
etc.................