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Medical biology, microbiology, virology, immunology department by As.Prof. O.V. Pokryshko Microbial Mechanisms Microbial Mechanisms of Pathogenicity of Pathogenicity
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Medical biology, microbiology, virology, immunology department

Feb 09, 2016

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Medical biology, microbiology, virology, immunology department. Microbial Mechanisms of Pathogenicity. by As.Prof. O.V. Pokryshko. Main Features of Pathogenic Microorganisms. Pathogenicity. This is the potential capacity of certain species of microbes to cause an infectious process. - PowerPoint PPT Presentation
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Page 1: Medical biology, microbiology, virology, immunology department

Medical biology, microbiology, virology, immunology department

by As.Prof. O.V. Pokryshko

Microbial Mechanisms Microbial Mechanisms of Pathogenicityof Pathogenicity

Page 2: Medical biology, microbiology, virology, immunology department

Pathogenicity. This is the potential capacity of certain species of microbes to cause an infectious process.

Virulence signifies the degree of pathogenicity of the given culture (strain). Virulence, therefore, is an index of the qualitative individual nature of the pathogenic microorganism. Virulence in pathogenic microbes changes under the influence of natural conditions.

Main Features Main Features of Pathogenicof Pathogenic Microorganisms.Microorganisms.

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The virulence of pathogenic microorganisms is associated with

adherence, invasiveness, capsule production, toxin production, aggressiveness and other factors.

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The adherence

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Adherence factorAdherence factor DescriptionDescription Filamentous hemagglutinin

Causes adherence to erythrocytes

Fimbriae Help attach to solid bacteria to solid surfaces

Glycocalyx or capsule Inhibits phagocytosis and aids in adherence

Pili Bind bacteria together for transfer of genetic material

Slime Tenacious bacterial film that is less compact than a capsule

Teichoic and lipoteichoic acid

Cell wall components in gram positive bacteria that aid in adhesion

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Adherence bacteria to cell surfacesAdherence bacteria to cell surfaces

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Adherence of vibrio cholera on the mucoseAdherence of vibrio cholera on the mucose

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Capsule production

Capsule production Capsule production makes the microbes makes the microbes resistant toresistant to phagocytosisphagocytosis and and antibodiesantibodies, and , and increases their invasive increases their invasive properties. properties.

Thus, for example, Thus, for example, capsular capsular anthrax bacillianthrax bacilli are not subject to are not subject to phagocytosis, while phagocytosis, while noncapsular variants are noncapsular variants are easily phagocytized.easily phagocytized.

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The role of capsular material The role of capsular material in bacterial virulence.in bacterial virulence.

Some pathogenic microorganisms Some pathogenic microorganisms ((B.B. anthra anthraciscis, C, C.. perfringens, S. pneumo perfringens, S. pneumo--niae,niae, causative agents of causative agents of plague and plague and tularaemiatularaemia)) are capable of producing a are capable of producing a capsule in animal and human bodies. capsule in animal and human bodies. Certain microorganisms produce capsules Certain microorganisms produce capsules in the organism as well as in nutrient media in the organism as well as in nutrient media (causative agents of (causative agents of rhinoscleroma, rhinoscleroma, ozaena, pneumonia).ozaena, pneumonia).

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Virulent microbes are characterized by the ability to penetrate tissues of the infected organism (iinvasnvasiveive properties properties).

collagenase and hyaluronidase immunoglobulin A protease leukocidins M-protein protein A

InvasInvasiveive properties properties of pathogenic bacteriaof pathogenic bacteria

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Collagenase and hyaluronidase degrade collagen and hyaluronic acid, respectively, thereby allowing the bacteria to spread through subcutaneus tissue (Streptococci, Staphylococci, Clostridium ).

Immunoglobulin A protease degrades IgA, allowing the organism to adhere to mucous membranes, and is produseed chiefly by N. gonorrhoeae, Haemophilus influenzae, and S. pneumoniae.

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Leukocidins can destroy both neutrophilic leukocytes and macrophages.

M-protein of S. pyogenes is

antiphagocytic.

Protein A of S. aureus binds to IgG and prevents the activation of complement.

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Coagulase, which is produced by S. aureus and accelerate the formation of a fibrin clot from its precursor, fibrinogen (this clot may protect the bacteria from phagocytosis by walling off the infected area and by coating the organisms with a layer of fibrin)

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The invasion of cells by bacteria

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According to the nature of production, According to the nature of production, microbial toxins are subdivided into microbial toxins are subdivided into exotoxins and endotoxexotoxins and endotoxinsins. .

More than 50 protein exotoxins of bacteria are known to date.

Toxin production

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Exotoxins easily diffuse from the cell into the surrounding nutrient medium.

They are characterized by a markedly distinct toxicity, and act on the susceptible organism in very small doses.

Exotoxins have the properties of enzymes hydrolysing vitally important components of the cells of tissues and organs.

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Exotoxins exert their effects in a

variety of ways – by inhibition of protein

synthesis, inhibition of nerve synapse

function, disruption of membrane trans-

port, damage to plasma membranes.

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ExotoxinsExotoxins may be devided into fifth may be devided into fifth categories on the basis of the site affected:categories on the basis of the site affected:

neurotoxinsneurotoxins (tetanotoxin, botulotoxin) C. tetani, C. botulinum, B. cereus, S. aureus;

cytotoxinscytotoxins (enterotoxins, dermatonecrotoxin)E. coli, Salmonella spp., Klebsiella spp., V. cholerae, C. perfringens;

functional blocatorsfunctional blocators (cholerogen), V. cholerae;

membranotoxinsmembranotoxins (hemolysins, leucocidin), S. aureus;

exfoliatinexfoliatin S. aureus.

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Action of the hemolysin on red blood cellsAction of the hemolysin on red blood cells

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MICROORGANISM TOXIN DISEASE ACTION

Clostridium botulinum

Several neurotoxins

Botulism Paralysis; blocks neural transmission

Clostridium tetani Neurotoxin Tetanus Spastic paralysis; interferes with motor neurons

Corynebacterium diphtheriae

Cytotoxin Diphtheria 

Blocks protein synthesis

Bordetella pertussis

Pertussis toxin

Whooping cough Blocks G proteins that are involved in regulation of cell pathways

Streptococcus pyogenes

Hemolysin  

Scarlet fever Food Lysis of blood cells

Staphylococcus aureus

Enterotoxin Poisoning Intestinal inflammation

Aspergillus flavus Cytotoxin Aflatoxicosis Blocks transcription of DNA, thereby stopping protein synthesis

Amanita phalloides

Cytotoxin Mushroom food poisoning

Blocks transcription of DNA,thereby stopping protein synthesis

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Endotoxinsare more firmly bound with the body of the

bacterial cell, are less toxic and act on the

organism in large doses; their latent period is usually

estimated in hours, the selective action is poorly

expressed.

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According to chemical structure, endotoxins are related to glucoside-lipid and polysaccharide compounds or phospholipid-protein complexes.

They are thermostable. Some endotoxins withstand boiling and autoclaving at 120°C for 30 minutes.

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Action of the endotoxinAction of the endotoxin

Endotoxin in the bloodstream

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Differences between exotoxins and endotoxinsDifferences between exotoxins and endotoxins

exotoxinsexotoxins endotoxinsendotoxinsProteinsProteins LipopolysaccharidesLipopolysaccharidesHeat labileHeat labile Heat stableHeat stableActively secreted by cells, Actively secreted by cells, diffuse into surrounding diffuse into surrounding mediummedium

form part of cell wall,do form part of cell wall,do not diffuse into not diffuse into surrounding mediumsurrounding medium

Readily separable from Readily separable from cultures by physical cultures by physical means such as filtrationmeans such as filtration

Obtained only by cell Obtained only by cell lysinglysing

Action often enzymicAction often enzymic No enzymic actionNo enzymic actionSpecific pharmacological Specific pharmacological effect for each exotoxineffect for each exotoxin

Non-specific action of all Non-specific action of all endotoxinsendotoxins

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Specific tissue affinitiesSpecific tissue affinities No specific tissue affinityNo specific tissue affinityActive in very minute Active in very minute dosesdoses

Active only in very large Active only in very large dosesdoses

Highly antigenicHighly antigenic Weakly antigenicWeakly antigenic

Stimulate formation of Stimulate formation of antitoxin which neutralizes antitoxin which neutralizes toxintoxin

Do not stimulate formation Do not stimulate formation of antitoxinof antitoxin

Converted into toxoid by Converted into toxoid by formaldehydeformaldehyde

Can not be toxoidedCan not be toxoided

Produced by both gram-Produced by both gram-positive bacteria and positive bacteria and gram-negative bacteriagram-negative bacteria

Produced by gram-Produced by gram-negative bacteria onlynegative bacteria only

Frequently controlled by Frequently controlled by extrachromosomal genes extrachromosomal genes (e.g. plasmids)(e.g. plasmids)

Synthesis directed by Synthesis directed by chromosomal genes chromosomal genes genesgenes

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In characterizing pathogenic microbes a unit of virulence has been established.

Dlm (Dosis letalis minima), representing the minimum amount of live microbes which in a certain period of time bring about 95-97 % death of the corresponding laboratory animals.

the absolute lethal dose of pathogenic microbe Dcl (Dosis certa letalis) which will kill 100 % of the experimental animals has been established.

At present LD50 (the dose which is lethal to one half of the infected animals) is considered to be the most suitable, and may serve as an objective criterion for comparison with other units of virulence.