Medical biology, microbiology, virology, immunology department
by As.Prof. O.V. Pokryshko
Microbial Mechanisms Microbial Mechanisms of Pathogenicityof Pathogenicity
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.
The virulence of pathogenic microorganisms is associated with
adherence, invasiveness, capsule production, toxin production, aggressiveness and other factors.
The adherence
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
Adherence bacteria to cell surfacesAdherence bacteria to cell surfaces
Adherence of vibrio cholera on the mucoseAdherence of vibrio cholera on the mucose
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.
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).
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
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.
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.
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)
The invasion of cells by bacteria
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
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.
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.
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.
Action of the hemolysin on red blood cellsAction of the hemolysin on red blood cells
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
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.
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.
Action of the endotoxinAction of the endotoxin
Endotoxin in the bloodstream
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
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
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.