Medical biology, microbiology, virology, immunology department

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

2. Main Features of PathogenicMicroorganisms. Pathogenicity.This is the potential capacity of certain species of microbes to cause an infectious process. Virulencesignifies 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.

3. The virulence of pathogenic microorganisms is associated with • adherence, • invasiveness, • capsule production, • toxin production, • aggressiveness • and other factors.

4. The adherence

6. Adherence bacteria to cell surfaces

8. Adherence of vibrio cholera on the mucose

9. Capsule production Capsule production makes the microbes resistant tophagocytosis and antibodies, and increases their invasive properties. Thus, for example, capsular anthrax bacilli are not subject to phagocytosis, while noncapsular variants are easily phagocytized.

10. 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).

11. Invasive propertiesof pathogenic bacteria • Virulent microbes are characterized bythe ability to penetrate tissues of the infected organism (invasive properties). • collagenase and hyaluronidase • immunoglobulin A protease • leukocidins • M-protein • protein A

12. 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.

13. 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.

14. 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)

16. The invasion of cells by bacteria

17. Toxin production 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.

18. 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.

19. Exotoxinsexert 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.

20. 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; • exfoliatinS. aureus.

21. Action of the hemolysin on red blood cells

22. 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 foodpoisoning Blocks transcription of DNA,thereby stopping protein synthesis

25. 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.

26. 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.

28. Action of the endotoxin Endotoxin in the bloodstream

29. Differences between exotoxins and endotoxins

31. 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.