Microbial Mechanisms of Pathogenicity

Microbial Mechanisms 

of 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 

of Pathogenic Microorganisms.

The virulence of pathogenic microorganisms is associated with

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

The adherence

Adherence factor

 

Description

 

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 surfaces

Adherence of vibrio cholera on  the mucose

Capsule production

 

Capsule production makes the microbes resistant to phagocytosis and antibodies, and increases their invasive properties.

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

The role of capsular material  
in bacterial virulence.

 

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

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

 

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

 

Invasive properties of 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, microbial toxins are subdivided  into exotoxins and endotoxins.

 

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.

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

 

• neurotoxins (tetanotoxin, botulotoxin)  
  C. tetani, C. botulinum, B. cereus, S. aureus;
• cytotoxins (enterotoxins, dermatonecrotoxin) 
  E. coli, Salmonella spp., Klebsiella spp., V. cholerae, C. perfringens;
• functional blocators (cholerogen),  
  V. cholerae;
• membranotoxins (hemolysins, leucocidin),  
  S. aureus;
• exfoliatin  
  S. aureus.

Action 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

 

Endotoxins

 

• are 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 endotoxin

 

Endotoxin in the bloodstream

Differences between exotoxins and  endotoxins

 

exotoxins

 

endotoxins

 

Proteins

 

Lipopolysaccharides

 

Heat labile

 

Heat stable

 

Actively secreted by cells, diffuse  into surrounding medium

 

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

 

Readily separable from cultures  by physical means  such as filtration

 

Obtained only by cell lysing

 

Action often enzymic

 

No enzymic action

 

Specific pharmacological effect for  each exotoxin

 

Non-specific action of all endotoxins

Specific tissue affinities

 

No specific tissue affinity

 

Active in very minute doses

 

Active only in very large  doses

 

Highly antigenic

 

Weakly antigenic

 

Stimulate formation of antitoxin  which neutralizes toxin

 

Do not stimulate formation of  antitoxin

 

Converted into toxoid by formaldehyde

 

Can not be toxoided

 

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

 

Produced by gram-negative bacteria  only

 

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

 

Synthesis directed by chromosomal  genes genes

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.

 

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