The virulence of microbes is not constant. The change in virulence can be phenotypic and genotypic. So, virulence can change phenotypically depending on the age of the culture, growing temperature, which is associated with the inductive nature of the synthesis of some biologically active substances (temperature-dependent synthesis of a number of antigens of plague bacilli, Vi-antigen of typhoid bacteria, some enzymes).

The virulence of a microorganism can be increased or decreased by artificial means.

Long-term cultivation of cultures outside the body on ordinary nutrient media, cultivation of cultures at maximum temperature (experiments by L. Pasteur and L. S. Tsenkovsky), addition of antiseptic substances to cultures (potassium dichromate, carbolic acid, alkali, sublimate, bile, etc.). ) weaken the virulence of microorganisms. Based on this principle, attenuated live vaccines are prepared, which are then used against infectious diseases. The virulence of the microbe can also decrease in natural conditions under the influence of sunlight, drying, etc.

Passaging (successive conduction) of the causative agent of any infectious disease through a certain type of animal from an infected to a healthy one, for example, the causative agent of swine erysipelas through the body of a rabbit, weakens the virulence for pigs, but enhances it for the rabbits themselves. The action of a bacteriophage (biological factor) can lead to a weakening of the virulence of microorganisms. Under natural conditions, the virulence of bacteria increases by passage through a susceptible organism, so animals with a contagious disease must be immediately isolated from healthy ones.

Strengthening of virulence under the action of proteolytic enzymes can be observed in Cl. perfringens by natural association with putrefactive agents (eg, sarcins) or by artificial exposure to an animal-derived enzyme (eg, trypsin).

This effect is associated with the ability of proteases to activate protoxins, i.e., precursors of epsilon toxin types B and D and iota toxin type E Cl. perfringens.

Thus, virulence as a measure of pathogenicity is a variable value. It can be raised, lowered and even lost.

Stable loss of pathogenic properties is defined by the concept of " avirulence". A decrease (attenuation) or a complete loss of virulence is observed when reseeding cultures in laboratory conditions and under the influence of various physicochemical and biological factors. Complete loss of virulence, as well as attenuation, is associated with a change in the genotype of the strain.

The genetic factors that determine virulence have so far been studied only in some pathogenic microorganisms. Chromosomal mapping of such factors and knowledge of markers that correlate with virulence will allow in the future short time to obtain strains with the characteristics necessary for microbiologists.

Virulence measurement

Pathogenicity and virulence are not synonymous. A microorganism is considered virulent if it, when introduced into the body of an animal, even in extremely small doses, leads to the development of an infectious process. No one doubts the pathogenicity of the anthrax bacillus, meanwhile, among the cultures of this microbe, occasionally, but there are avirulent strains that are not capable of causing disease in sheep and even rabbits. Pig erysipelas bacteria belong to a pathogenic species, but many varieties of this microbe have been isolated from the body of perfectly healthy pigs, turkeys, and fish.

Lethal and infectious doses are conventionally taken as the unit of measurement of virulence. The minimum lethal dose - DLM (Dosis letalis minima) is the smallest amount of living microbes or their toxins that causes the death of most animals of a certain species taken in the experiment over a certain period of time. But since the individual sensitivity of animals to a pathogenic microbe (toxin) is different, an unconditionally lethal dose was introduced - DCL (Dosis certa letalis), which causes the death of 100% of infected animals. The most accurate is the average lethal dose - LD 50, i.e. the smallest dose of microbes (toxins) that kills half of the animals in the experiment. To establish a lethal dose, one should take into account the method of administration of the pathogen, as well as the weight and age of the experimental animals, for example, white mice 16-18 g, guinea pigs - 350 g, rabbits - 2 kg. In the same way, the infectious dose (ID), i.e., the amount of microbes or their toxins that causes the corresponding infectious disease, is determined.

Highly virulent microorganisms can cause disease in animals or humans in the smallest doses. For example, it is known that 2-3 Mycobacterium tuberculosis, when injected into the trachea, causes fatal tuberculosis in a guinea pig. Virulent strains of anthrax bacilli in the amount of 1-2 cells can cause death in guinea pig, a white mouse and even a large animal.

To quantify the degree of pathogenicity of a microorganism, the term virulence is used, which is measured in conditionally accepted units– DLM,DcL,DL 50 .DLM(Dosisletalisminima) is the minimum lethal dose of microorganisms that causes the death of 95% of susceptible laboratory animals. DL 50 causes the death of 50% of infected animals, DcL is a lethal dose that causes the death of all animals.

The degree of pathogenicity of a microorganism depends on many factors and is due both to the presence of enzyme systems that ensure the existence of the pathogen in the macroorganism, and its ability to withstand the body's defense factors aimed at destroying the pathogen. According to the degree of pathogenicity, pathogenic and conditionally pathogenic microorganisms are distinguished. Pathogenic microorganisms are capable, in most cases, of causing an infectious process, and opportunistic microorganisms, often natural inhabitants of the human body, cause diseases only when immunity is reduced and the infectious dose is sufficiently large. The degree of pathogenicity of a microorganism is associated with its ability to adhere, colonize, invade, suppress phagocytosis, and other factors.

Pathogenicity factors include the ability of microorganisms to attach to cells (adhesion), settle on their surface (colonization), penetrate cells (invasion), and resist the body's defense factors (aggression).

Adhesion is the starting mechanism of the infectious process. Adhesion is understood as the ability of a microorganism to be adsorbed on sensitive cells with subsequent colonization. The structures responsible for binding a microorganism to a cell are called adhesins and they are located on its surface. Adhesins are very diverse in structure and cause high specificity - the ability of some microorganisms to attach to the epithelial cells of the respiratory tract, others - of the intestinal tract or genitourinary system, etc. The adhesion process can be influenced by physicochemical mechanisms associated with the hydrophobicity of microbial cells, the sum of the energy of attraction and repulsion. In gram-negative bacteria, adhesion occurs due to pili general types. In Gram-positive bacteria, adhesins are proteins and teichoic acids of the cell wall. In other microorganisms, this function is performed by various structures of the cellular system: surface proteins, lipopolysaccharides, etc.

Invasion. Invasiveness is understood as the ability of microbes to penetrate through mucous membranes, skin, connective tissue barriers into internal environment organism and spread through its tissues and organs. The penetration of a microorganism into a cell is associated with the production of enzymes, as well as with factors that suppress cellular defense. So the enzyme hyaluronidase breaks down hyaluronic acid, which is part of the intercellular substance, and thus increases the permeability of the mucous membranes and connective tissue. Neuraminidase breaks down neuraminic acid, which is part of the surface receptors of mucous membrane cells, which contributes to the penetration of the pathogen into tissues.

Aggression. Under the aggressiveness understand the ability of the pathogen to resist the protective factors of the macroorganism. Aggression factors include: proteases - enzymes that destroy immunoglobulins; coagulase - an enzyme that coagulates blood plasma; fibrinolysin - dissolving fibrin clot; lecithinase is an enzyme that acts on the phospholipids of the membranes of muscle fibers, erythrocytes and other cells. Pathogenicity can also be associated with other enzymes of microorganisms, while they act both locally and generalized.

Toxins play an important role in the development of the infectious process. According to their biological properties, bacterial toxins are divided into exotoxins and endotoxins. Exotoxins produce both Gram-positive and Gram-negative bacteria. According to their chemical structure, they are proteins. According to the mechanism of action of exotoxin on the cell, several types are distinguished: cytotoxins, membrane toxins, functional blockers, exfoliants and erythrohemins. The mechanism of action of protein toxins is reduced to damage to vital processes in the cell: increased membrane permeability, blockade of protein synthesis and other biochemical processes in the cell, or disruption of interaction and coordination between cells. Exotoxins are strong antigens that produce the formation of antitoxins in the body.

According to their molecular organization, exotoxins are divided into two groups:

    exotoxins consisting of two fragments;

    exotoxins that make up a single polypeptide chain.

According to the degree of connection with the bacterial cell, exotoxins are conditionally divided into three classes.

    Class A - toxins secreted into the external environment;

    Class B - toxins partially secreted and partially associated with the microbial cell;

    Class C - toxins associated with the microbial cell and entering the environment upon cell destruction.

Exotoxins are highly toxic. Under the influence of formalin and temperature, exotoxins lose their toxicity, but retain their immunogenic properties. Such toxins are called toxoids and are used to prevent tetanus, gangrene, botulism, diphtheria, and are also used as antigens for animal immunization in order to obtain toxoid sera.

Endotoxins in their chemical structure, they are lipopolysaccharides, which are contained in the cell wall of gram-negative bacteria and are released into the environment during bacterial lysis. Endotoxins do not have specificity, are thermostable, less toxic, and have weak immunogenicity. When large doses enter the body, endotoxins inhibit phagocytosis, granulocytosis, monocytosis, increase capillary permeability, and have a destructive effect on cells. Microbial lipopolysaccharides destroy blood leukocytes, cause degranulation of mast cells with the release of vasodilators, activate the Hageman factor, which leads to leukopenia, hyperthermia, hypotension, acidosis, and disseminated intravascular coagulation (DVC).

Endotoxins stimulate the synthesis of interferons, activate the complement system in the classical way, and have allergic properties.

With the introduction of small doses of endotoxin, the body's resistance increases, phagocytosis increases, and B-lymphocytes are stimulated. The serum of an animal immunized with endotoxin has weak antitoxic activity and does not neutralize endotoxin.

The pathogenicity of bacteria is controlled by three types of genes: genes - by their own chromosomes, genes introduced by plasmids by temperate phages.

THE DOCTRINE OF INFECTION in the history of the development of the doctrine there are 3 periods: l Miasmatic (even Hippocrates suggested the nature of contagious diseases "miasma" of small invisible animals) which causes illness. To protect against illness, they were recommended isolation of the patient, quarantine, wearing masks, treating objects with vinegar) l Microbiological (associated with the name of Louis Pasteur and the discoveries of R. Koch - Koch's triad)

INFECTION (lat. Infectio - infection) penetration of a microorganism into a macroorganism and its reproduction in it, resulting in an infectious process Historically, the word "infection" was first introduced to refer to sexually transmitted diseases

An infectious process is a process of interaction between a micro- and a macroorganism under certain environmental conditions IP can be represented by: l infectious disease l bacteriocarrier l vaccine process

An infectious process is a process of interaction between a micro- and a macroorganism under certain environmental conditions Asymptomatic: l bacteria carrying l "vaccine process" l l l With symptoms: infectious disease mild form of moderate severity severe form

Bacteriocarrier - there can be a healthy carrier (in contact with a patient or a carrier) and high resistance to pathogenic microbes l - acute carriage with a weak post-infectious immunity l - carriage when the pathogen practically does not harm the host, but, for example, carriage of staphylococcus phage group 3 by workers Food Industry is dangerous in terms of food contamination l - chronic carriage (dangerous with typhoid fever, viral hepatitis B) l

Vaccine process with a pronounced immune restructuring l - depending on the reactivity of the organism, symptoms may be present (during vaccination l - characterized by smallpox vaccine, symptoms characteristic of smallpox may appear at the injection site)

An infectious disease is the most pronounced form of an infectious process, characterized by: l the presence of a specific pathogen l incubation period l specific symptoms l immune response l the clinical picture (symptoms) can be pronounced with a staphylococcal infection, but may be accompanied by total absence characteristic symptoms (with brucellosis) Infectious diseases have a number of differences from somatic diseases: - the presence of a pathogen - contagiousness - cyclicity of the course , salmonellosis, etc.

Infectious disease Origin: l Form of manifestation: l Type of manifestation: l Course: Manifestations: exogenous and endogenous acute and chronic local (at the gates of infection) regional (lesion of l / nodes) general (pathogen in the blood) cyclic and acyclic manifest (characteristic symptom complex) asymptomatic (without severe symptoms) inapparent (symptoms are mild) abortive (with an incomplete set of symptoms)

Stages of the infectious process: l l l 1. Infection: the microbe enters the human body. If defense mechanisms organisms are sufficient, then the infectious process may stop at this stage 2. Incubation period: the time from the moment of penetration of mi / o until the appearance of 1 specific symptoms of the disease (lasts from several hours - toxic infection to several years - AIDS). Characterized by the presence common symptoms(malaise, decreased performance) 3. Prodromal period: the period of precursors, when specific symptoms of the disease appear and can quickly disappear at the same time (for example, Filatov-Belsky spots with measles) 4. The peak period of the disease 5. Outcome of the disease: recovery, transition to chronic form or bacteriocarrier, death.

Microbiological and immunological characteristics of periods of an infectious disease Incubation - adhesion of microorganisms on sensitive cells, the pathogen is not released into the environment, antibodies are not detected l Prodromal - colonization of sensitive cells, the pathogen is not released into the environment, antibodies are not detected l The height of the disease - intensive reproduction of the pathogen and release into the environment, Ig M antibodies are detected, then Ig G and Ig A l Reconvalescence - cessation of reproduction and death of the pathogen, cessation of release into the environment, an increase in the titer of Ig G and Ig A antibodies, the antibody titer reaches a maximum. The causative agent in many diseases is secreted in in large numbers l

An infectious disease does not occur every time a pathogenic microbe enters the human body l l Certain conditions are required for the implementation of IP: - a sufficient dose of microorganisms minimal amount microbial cells capable of causing IP). Plague - several bacterial cells, dysentery - dozens, for some pathogens - thousands - hundreds of thousands l - natural route of penetration - the entrance gate of infection, different for wound, respiratory, intestinal, urogenital infections with different mechanisms of infection (skin, respiratory tract, gastrointestinal tract, genitourinary system) l - characteristics of the pathogen, its pathogenic properties, the ability to overcome the host's defense mechanisms l - the state of the host organism (heredity, heterogeneity of the human population in terms of susceptibility to infection, sex, age, state of the immune, nervous and endocrine systems, lifestyle, natural and social conditions of life, etc.)

According to their ability to cause infection, microorganisms are divided into three groups: l 1. pathogenic - always cause infection (causative agents of classical infections) l 2. conditionally pathogenic - cause infection under certain conditions and in the 1st turn | with a decrease in the resistance of the macroorganism (causative agents of opportunistic infections ) l 3. non-pathogenic - saprophytes (incapable of causing infection)

Classification of microorganisms according to the degree of danger to humans l Plague causative agent l Cholera, anthrax, brucellosis, etc. pathogens l Tuberculosis, diphtheria, typhoid fever and other classical infections l UPM - staphylococci, clostridia, proteas and other causative agents of opportunistic infections

Pathogenic and conditionally pathogenic microorganisms have pathogenicity, i.e. potential, l genetically determined ability l to penetrate into the macroorganism and l multiply in it phenotypic expression pathogenicity is virulence - a measure of pathogenicity, a quantitative sign, consists of: aggressiveness, toxicity and toxigenicity

Virulence of microorganisms In order to cause an infectious disease, a pathogenic microorganism must have virulence, i.e. the ability not only l to penetrate the macroorganism, l multiply in it, but also l suppress its defense mechanisms Aggressiveness - the ability of a microorganism to penetrate into the human body, spread, multiply, suppress its defense mechanisms Infectivity - the ability to infect Invasiveness - the ability to penetrate

Virulence is a strain trait, l is a phenotypic manifestation of a pathogenic genotype l is a quantitative trait, measured by the dose of my/o causing a certain biological effect l is a labile trait that changes both upwards and downwards both in vitro and in vivo With a maximum decrease in virulence pathogenic microorganisms can become avirulent, but virulent ones are always pathogenic

Virulence is measured by: Absolute lethal dose of DCL (dosis certae letalis) l the minimum amount of the pathogen that causes the death of 100% of laboratory animals taken in the experiment l

Virulence is measured by: Minimum lethal dose - DLM (dosis letalis minima) - l - the minimum amount of pathogen that causes the death of 95% of laboratory animals taken in the experiment l

Virulence is realized through a number of successive processes of interaction of microbial cells with cells and tissues of a macroorganism: this is l adhesion - the ability to attach to cells, l colonization - the ability to multiply on their surface l invasion - the ability to penetrate underlying tissues, and also l the ability to form biologically active products, in including toxins into cells and

The starting point of IP is adhesion and colonization without adhesion to receptors of sensitive cells microorganisms do not multiply and are excreted from the macroorganism Adhesion mechanisms include: l the presence of fimbriae l hydrophilicity (ligand-receptor interaction between bacteria and host cells) l the presence of a capsule, and the mucous components of the cell membrane (protein Staphylococcus A, Streptococcus protein M)

Adhesins: in GR-bacteria, these are fimbriae (pili 1 or common type) and proteins of the outer membrane, l in GR+ bacteria, these are proteins and teichoic acids of the cell wall, l in mycoplasmas, macromolecules that make up outgrowths plasma membrane, l in viruses - hemagglutinins l the ability to attach to the epithelial cells of the mucous membrane of the upper respiratory tract, intestines, skin in some cases is a defining feature, for example, viruses, bacteria of the intestinal group: vibrio cholerae, salmonella - if they lose their adhesiveness, they lose the ability to cause a pathological process

Polysaccharide capsule (in meningococcus) or protein (in pneumococcus); performs the following functions: l - closes the antigenic structures of the bacterium, making it invisible to phagocytes, complement l - in the case of phagocytosis, the mucous layer or capsule is separated from the cell and it is them that are captured by the phagocyte, and not the bacteria l - if the phagocyte captures the cell itself, it does not occur its digestion, because lysosomes are not able to destroy the structures of capsules

To implement colonization and invasion, bacteria secrete aggression and defense enzymes: l neuraminidase (sialidase) - breaks down neuraminic (sialic) acid, increasing the permeability of various tissues, helps mi / o to penetrate through the thick mucous layer into the eukaryotic cell l hyaluronidase - facilitates the penetration of mi / o deep into tissues hydrolyzes hyaluronic acid - the main intercellular substance of connective tissue - fibrinolysin (streptokinase) - a proteolytic enzyme, dissolves a fibrin clot that forms during inflammation and prevents the penetration of mi / o deep into tissues and organs, thereby facilitating the invasion of mi / o l plasmocoagulase, causes the formation fibrin barriers

Plasmocoagulase l l l causes plasma coagulation in vitro and in vivo in capillaries, arterioles, venules; forms a film of fibrin on the surface of the bacterium, making it invisible to the host's immune system! prevents the digestion of bacteria inside the phagocyte - the phenomenon of incomplete phagocytosis! causes the formation of blood clots in the vessels of the MCR, forming a focus into which antibodies, complement, leukocytes do not penetrate, a tissue area with a sharply reduced metabolism is created

Determination of the presence of plasma coagulase Coagulase test: l - culture of Staphylococcus aureus is introduced into a test tube with citrate plasma, l - after incubation in a thermostat, the plasma has curtailed, l - it has remained liquid in the control tube. l

To suppress the immune system, microorganisms produce: proteases - destroy antibodies l lecithinase - destroys cell membrane lecithin l antiphagin - lipopolysaccharide, has toxic effect on phagocytes Proteases, lipases, saccharolytic enzymes carry out tissue splitting at the site of the pathogen localization l A significant factor in invasiveness is the mobility of bacteria, which determines the penetration of microbes into cells and into intercellular spaces.

Aggressiveness refers to the ability to stay at the penetration sites of colonization resistance in tissues: - l Aggressins cause negative chemotaxis (phagocytes leave the site of penetration of mi / o) l Colicinogenicity - the ability of mi / o to secrete bacteriocins substances that suppress bacteria - antagonists, representatives of the normoflora Hp. : more severe dysentery caused by shigella that secrete colicins (25% of Flexner's shigella secrete colicins. Without colicins, they are less dangerous than shigella dysentery, and with colicins, they can cause fatal dysentery in children)

2 more mechanisms of virulence: Toxicity - the toxicity of the anatomical structures of the cell, i.e. the presence of endotoxin - released only when the mi/o is destroyed. This is a complex of LPS with a protein located in the cytoplasm, CPM and membrane, (part of the lipids and polysaccharides are on the cell surface) l Toxigenicity is the ability of my / o to produce a toxin and release it into the environment, i.e. the presence of exotoxin. This is a protein of 2 chains: receptor (carrier protein that carries the toxin to the receptor sites of the target cell and is adsorbed on their surface) and activator (highly specific part responsible for the toxic effect) l

Exotoxins are true toxins: diphtheria, tetanus, botulinum toxin - are the leading factors in the development of diseases, the strength of toxins is measured in DLM or LD 5 o l l l l Exotoxins are proteins, thermolabile (T +) are usually produced by Gr + bacteria, have a specific effect ( Sp +) have a latent period de-I (Lp +) are strong antigens (I +) with special. processed into toxoids (A +)

Endotoxins l are LPS with protein l are thermostable (T-) l are produced, as a rule, by Gr-bacteria l have a general toxic effect (Sp-) l do not have a latent period of action (Lp-) l are weak antigens (I-) l do not pass in toxoid (A-) l insensitive to chemical. substances (F-)

Producers of exotoxins l among Gr+ bacteria: causative agents of diphtheria, botulism, tetanus, gas gangrene, some types of staphylococci and streptococci l among Gr-bacteria: cholera vibrio, some types of pseudomonads (Ps. aeruginosa) and shigella (Grigorieva-Shiga)

Production of exotoxins l The ability to produce exotoxin can be acquired through the transfer of information by a plasmid or temperate phage (for example, diphtheria bacillus is toxigenic only when it is lysogenic, that is, when it contains a prophage in its cytoplasm that carries information about the synthesis of the receptor part of the toxin) l Genes, contained in the chromosome and determining virulence are called tox-genes (plasmids - ent).

Pathogenicity factors are controlled by: l-chromosome genes l-plasmid genes l-genes introduced by temperate phages

Formation of toxins l Many bacteria form not one, but several protein toxins that have different action: neurotoxic, cytotoxic, hemolytic, for example, staphylococcus aureus, streptococcus. l Some - can simultaneously form both protein exotoxins and endotoxins, for example, E. coli, Vibrio cholerae.

Invasiveness and toxigenicity All virulence factors are closely and inextricably linked; but l pathogens of OOI: anthrax, plague, tularemia, brucellosis have a very high invasiveness and can quickly penetrate even through intact skin into tissues and multiply intensively in them l pathogens of diphtheria and tetanus are characterized by high toxigenicity, which is decisive in the clinical picture, and very weak invasiveness, as a result of which they do not spread in the body Toxigenicity and invasiveness have independent genetic control, often are inversely related (a pathogen with high toxigenicity may have low invasiveness and vice versa)

According to the mechanism of action on the cells of the macroorganism, toxins are released: membranotoxins - hemolysins, leukocidins l functional blockers or neurotoxins (tetanospasmin, botulinum toxin), blocking the transmission of nerve impulses in the cells of the spinal cord and brain l l cytotoxins - blocking protein synthesis at the subcellular level: enterotoxin Staphylococcus aureus, dermonecrotoxins of streptococci, anthrax, blue-green pus and whooping cough

According to the mechanism of action on the cells of the macroorganism, toxins l enterotoxins are released - thermolabile and thermostable, activate cellular adenylate cyclase, which leads to an increase in the permeability of the small intestine wall and an increase in the release of fluid into the intestinal lumen - diarrhea, they are produced by V. cholerae (cholerogen), enterotoxigenic E. coli l exfoliatins - formed by some strains of S. aureus, and erythrogenins produced by Str. pyogenes group A. They affect the process of interaction of cells with each other and with intercellular substances and completely determine the clinical picture of the infection. In the first case, pemphigus of newborns occurs, in the second - scarlet fever - anti-elongators - prevent elongation (build-up) or translocation, i.e., the movement of mRNA along the ribosome, and thereby block protein synthesis. These include diphtheria histotoxin, Pseudomonas aeruginosa toxin

MAIN DIRECTIONS æ Quality improvement medical care population, development of standards and criteria for assessing the quality medical care; æ Combat infectious diseases, ensuring the biological security of the country; æ Maternal and child health; æ Provision of medical institutions with modern medical equipment, diagnostic and medicinal preparations.

11 pathogens 1972 - 1981 Ebola virus, Hunt virus, Legionella pneumoniae 13 pathogens 1982 - 1991 HIV - the causative agent of AIDS hepatitis E virus

13 pathogens 1992 - 2001 Coronavirus - the causative agent of severe acute respiratory syndrome (SARS) Virus bird flu type A (H 7 N 7) Prions pathogenic for humans Avian influenza virus type A (H 5 N 1) 2 pathogens 2002 – 2004

In total for the period 1972 - 2006 (32 years), 39 new pathogens were isolated and identified

35 Pathogenicity and virulence of bacteria. Pathogenic, conditionally pathogenic and saprophytic microorganisms. pathogenicity factors.

Bacteria are distinguished by their ability to cause disease:

1) pathogenic;

2) conditionally pathogenic;

Pathogenic species have the potential to cause an infectious disease.

Pathogenicity is the ability of microorganisms, entering the body, to cause pathological changes in its tissues and organs. This is a qualitative species trait determined by pathogenicity genes - virulons. They can be localized in chromosomes, plasmids, transposons.

Opportunistic bacteria can cause an infectious disease with a decrease in the body's defenses.

Saprophytic bactors never cause disease, since they are not able to multiply in the tissues of the macroorganism.

The implementation of pathogenicity goes through virulence - this is the ability of a microorganism to penetrate into a macroorganism, multiply in it and suppress its protective properties.

This is a strain trait, it can be quantified. Virulence is the phenotypic manifestation of pathogenicity.

The quantitative characteristics of virulence are:

1) DLM (minimum lethal dose) is the amount of bacteria, which, when introduced into the body of laboratory animals in an appropriate way, results in 95–98% of the death of animals in the experiment;

2) LD 50 is the number of bacteria that causes the death of 50% of the animals in the experiment;

3) DCL (lethal dose) causes 100% death of animals in the experiment.

Virulence factors include:

1) adhesion - the ability of bacteria to attach to epithelial cells. Adhesion factors are adhesion cilia, adhesive proteins, lipopolysaccharides in gram-negative bacteria, teichoic acids in gram-positive bacteria, in viruses - specific structures of a protein or polysaccharide nature;

2) colonization - the ability to multiply on the surface of cells, which leads to the accumulation of bacteria;

3) penetration - the ability to penetrate cells;

4) invasion - the ability to penetrate into the underlying tissues. This ability is associated with the production of enzymes such as hyaluronidase and neuraminidase;

5) aggression - the ability to resist the factors of nonspecific and immune defense of the body.

The phenotypic feature of a pathogenic microorganism is its virulence, those. a property of a strain that manifests itself under certain conditions (with the variability of microorganisms, changes in the susceptibility of a macroorganism, etc.). Virulence can be increased, decreased, measured, i.e. she is a measure of pathogenicity. Quantitative indicators of virulence can be expressed in DLM (minimum lethal dose), DL" (dose that causes the death of 50% of experimental animals). At the same time, the type of animals, sex, body weight, method of infection, time of death are taken into account.

Pathogenicity factors include the ability of microorganisms to attach to cells (adhesion), settle on their surface (colonization), penetrate cells (invasion), and resist the body's defense factors (aggression).

Adhesionis the starting mechanism of the infectious process. Adhesion is understood as the ability of a microorganism to be adsorbed on sensitive cells with subsequent colonization. The structures responsible for binding a microorganism to a cell are called adhesins and they are located on its surface.

Adhesins are very diverse in structure and cause high specificity - the ability of some microorganisms to attach to the epithelial cells of the respiratory tract, others - of the intestinal tract or genitourinary system, etc.

The adhesion process can be influenced by physicochemical mechanisms associated with the hydrophobicity of microbial cells, the sum of the energy of attraction and repulsion. In gram-negative bacteria, adhesion occurs due to pili I and common types. In Gram-positive bacteria, adhesins are proteins and teichoic acids of the cell wall. In other microorganisms, this function is performed by various structures of the cellular system: surface proteins, lipopolysaccharides, etc.

Invasion. Invasiveness is understood as the ability of microbes to penetrate through the mucous membranes, skin, connective tissue barriers into the internal environment of the body and spread through its tissues and organs. The penetration of a microorganism into a cell is associated with the production of enzymes, as well as with factors that suppress cellular defense. So ferment hyaluronidase breaks down hyaluronic acid acid, which is part of the intercellular substance, and thus increases the permeability of the mucous membranes and connective tissue. Neuraminidase breaks down neuraminic acid, which is part of the surface receptors of mucous membrane cells, which contributes to the penetration of the pathogen into tissues.

Aggression. Under the aggressiveness understand the ability of the pathogen to resist the protective factors of the macroorganism.

Aggressive factors include:

Hyaluropidase.The action of this enzyme is mainly reduced to increasing the permeability of tissues. Skin, subcutaneous tissue and intermuscular tissue contain mucopolysaccharides and hyaluronic acid, which slow down the penetration of foreign substances through these tissues, even in a liquid state. Hyaluronidase is able to break down mucopolysaccharides and hyaluronic acid, as a result of which the permeability of tissues increases and the microorganism freely moves into the deep tissues and organs of the animal body. This enzyme is synthesized by brucella, hemolytic streptococci, clostridia and other microorganisms.

fibrinolysis.Some strains of hemolytic streptococcus, staphylococcus, yersinia synthesize fibrinolysin, which dilutes dense blood clots (fibrin). Hyaluronidase and fibrinolysin increase the ability of pathogenic microbes to generalize the process and eliminate chemical and mechanical obstacles to the penetration of microbes into the depths of tissues.

Neuramipidasecleaves off from various carbohydrates the terminal sialic acids associated with them by a glycosidic bond, which depolymerize the corresponding surface structures of epithelial and other cells of the body, dilute the nasal secretion and the mucinous layer of the intestine. It is synthesized by Pastsrell, Yersinia, some Clostridia, Strepto-, diplococci, Vibrios etc.

DNases (deoxyribonuclease) depolymerize nucleic acid, which usually appears when leukocytes are destroyed in an inflammatory focus at the site of microbial invasion. The enzyme is produced by staphylococci, streptococci, clostridia and some other microbes.

collagenasehydrolyzes peptides containing proline that are part of collagen, gelatin and other compounds. As a result of the splitting of collagen structures, melting occurs

By muscle tissue. They produce the enzyme Clostridium malignant edema, especially strongly Clostridium histolyticum.

Coagulase.Citrated or oxalated blood plasma of humans and animals is rapidly coagulated by virulent strains of Staphylococcus aureus, and some strains of Escherichia coli and hay bacillus have the same property. Clotting of citrate or oxalate blood occurs due to the production of the coagulase enzyme by the listed microorganisms.

Pathogenicity can also be associated with other enzymes of microorganisms, while they act both locally and generalized.

An important role in the development of the infectious process playing toxins. By biological properties Bacterial toxins are divided into exotoxins and endotoxins.

Exotoxins produce both Gram-positive and Gram-negative bacteria. According to their chemical structure, they are proteins. According to the mechanism of action of exotoxin on the cell, several types are distinguished: cytotoxins, membrane toxins, functional blockers, exfoliants and erythrohemins.

The mechanism of action of protein toxins is reduced to damage to vital processes in the cell: increased membrane permeability, blockade of protein synthesis and other biochemical processes in the cell, or disruption of interaction and coordination between cells.

Exotoxins are strong antigens that produce the formation of antitoxins in the body. Exotoxins are highly toxic. Under the influence of formalin and temperature, exotoxins lose their toxicity, but retain their immunogenic properties. Such toxins are called toxoids and are used to prevent tetanus, gangrene, botulism, diphtheria, and are also used as antigens for animal immunization in order to obtain toxoid sera.

Endotoxins according to their chemical structure are polysaccharides and, which are contained in the cell wall of gram-negative bacteria and are released into the environment during bacterial lysis.

Endotoxins do not have specificity, are thermostable, less toxic, and have weak immunogenicity. When large doses enter the body, endotoxins inhibit phagocytosis, granulocytosis, monocytosis, increase capillary permeability, and have a destructive effect on cells. Microbial lipopolysaccharides destroy blood leukocytes, cause degranulation of mast cells with the release of vasodilators, activate the Hageman factor, which leads to leukopenia, hyperthermia, hypotension, acidosis, and disseminated intravascular coagulation (DVC).

Endotoxins stimulate the synthesis of interferons, activate the complement system in the classical way, and have allergic properties.

With the introduction of small doses of endotoxin, the body's resistance increases, phagocytosis increases, and B-lymphocytes are stimulated. The serum of an animal immunized with endotoxin has weak antitoxic activity and does not neutralize endotoxin. The pathogenicity of bacteria is controlled by three types of genes: genes - by their own chromosomes, genes introduced by plasmids by temperate phages.

Pathogenicity 4

Pathogenicity characteristic 4

Pathogenic microorganisms 5

Virulence 7

Change in virulence 8

Virulence measurement 9

Virulence Factors 10

Pathogenicity and virulence factors 11

Enzymes 12

Colonization 14

Adhesion 14

Colonization and penetration 16

Antiphages 17

Toxins 18

Chemical nature 20

Chemical composition 25

Mechanism of action 26

Conclusion 29

References 30

Introduction

In the course of evolutionary development, pathogens have adapted to grow in various tissues of the host. The high degree of specificity inherent in many microorganisms reflects differences in the biochemical composition of organs.

Infection is a complex biological process that occurs as a result of the penetration of pathogenic microbes into the body and the violation of the constancy of its internal environment.

In order for an infectious disease to occur, it is necessary to have a pathogen that has pathogenicity in general and virulence in particular.

The purpose of this work is to accumulate and systematize knowledge about the pathogenicity and virulence of bacteria and other microorganisms. Understanding the processes occurring in the animal body due to the action of pathogenicity factors is necessary to determine the causes of the disease and prescribe competent and effective treatment.

pathogenicity

pathogenicity microorganisms (gr. pathos - suffering, disease + gennao - create, produce; syn. disease) - a specific genetic trait, the potential to cause an infectious process under favorable conditions, the ability of microorganisms to take root in the tissues of the host organism, multiplying in them, causing pathological changes.

Characterization of pathogenicity

Pathogenicity is a polydeterminant genotypic trait that characterizes the ability of microorganisms to cause infection. This trait is controlled by a cluster of genes responsible for the formation of a number of bacterial cell structures (capsule, cell wall), enzymes that violate the integrity of tissues, and toxins. The phenotypic realization of the genotype that determines pathogenicity occurs only in a certain environment - in a susceptible organism. In an immune organism, pathogenicity remains unrealized.

Pathogenicity is characterized by specificity, i.e. the ability to cause pathomorphological and pathophysiological changes typical for this type of pathogen in certain tissues and organs with its natural methods of infection. In a susceptible organism, pathogenicity manifests itself in the form of a certain nosological form of infection and specific pathological changes in organs and tissues corresponding to the pathogenetic and clinical type of infections: purulent, respiratory, intestinal, etc. Thus, tubercle bacillus causes tuberculosis, vibrio cholerae causes cholera, etc. . As early as the 19th century, this gave F. Henle, and then R. Koch, the basis for formulating the so-called Henle-Koch triad. It lies in the fact that the etiological role of a microbe in a certain disease is recognized only when it satisfies three requirements:

    occurs only in this disease and is not isolated from healthy organisms or patients with other diseases;

    can be isolated in pure culture;

    a pure culture of this microbe causes in the experiment a disease similar to that of which it is suspected to be the causative agent.

Practice has shown that all three requirements are of relative importance.

Pathogenicity as a special quality of a pathogenic type of microbe is manifested in its aggressive properties and in its toxic effect on the body. Aggressiveness- this is the ability of a pathogenic microbe to live, multiply and spread in the body, to resist the adverse effects exerted by the body. Some pathogenic microbes, multiplying in the body or on culture medium in vitro, produce soluble products called aggressiveins. The purpose of aggressins is to suppress the action of phagocytes. Aggressins themselves are harmless to the body, but if they are added to a non-lethal dose of a culture of the corresponding microbe, they cause a fatal infection.