10.4.23.pathogenesis of bacterial infections.pptx

For mbbs and nursing

1. General Bacteriology: Pathogenesis of Bacterial Diseases

2. MECHANISM OF MICROBIAL PATHOGENICITY 2

3. MECHANISM OF MICROBIAL PATHOGENICITY 3 Pathogenicity - refer to the ability of a microbial species to produce disease. Virulence - relative degree of pathogenesis (tissue damage), which may vary between different strains of the same organism depending upon the expression of the virulence factors.

4. MECHANISM OF MICROBIAL PATHOGENICITY (Cont..) 4 Exaltation - Enhancement of virulence is known as exaltation, which can be induced experimentally by serial passage into susceptible hosts. Attenuation - Reduction of virulence which can be achieved by passage through unfavourable hosts, repeated cultures in artificial media, growth in high temperature or in the presence of weak antiseptics, desiccation or prolonged storage in culture.

5. Mode of transmission of bacterial infections 5 Transmission Bacterial agents/diseases Contact Multi-drug resistant organisms in hospitals such as S. aureus , E. coli , Klebsiella , etc. , Bacillus anthracis Droplet C. diphtheriae ,Pneumococcus , Meningococcus Aerosol M. tuberculosis Ingestion Salmonella and Shigella , Vibrio , Campylobacter ,Agents of food poisoning Vector-borne Rickettsiae , Borrelia Sexual Gonococcus , Chlamydia trachomatis , Treponema pallidum , Haemophilus ducryei Vertical Treponema pallidum Birth canal Listeria , Streptococcus agalactiae

6. Infective Dose 6 Minimum inoculum size that is capable of initiating an infection. Low infective dose: Shigella : Very low (as low as 10 bacilli) Escherichia coli O157: H7 (<10 bacilli) Campylobacter jejuni (500 bacilli).

7. Infective Dose (Cont..) 7 Large Infective dose Escherichia coli (10 6 - 10 8 bacilli) Salmonella (10 2 – 10 5 bacilli) Vibrio cholerae (10 6 - 10 8 bacilli).

8. Infective Dose (Cont..) 8 Infective dose varies depending upon the factors, such as: Virulence of the organism Host’s age and overall immune status Ability of the organism resisting the gastric acidity

9. Adhesion 9 Adhesion of the bacteria to body surfaces - initial event in the pathogenesis of the disease. Mediated by specialized molecules - adhesins - bind to specific host cell receptors. Adherence prevents the bacteria from being flushed away in secretions and also facilitates bacterial invasion into the host cells.

10. Adhesion (Cont..) 10 Structures which help in adhesion: Fimbriae or pili Non-pilus adhesins Biofilm formation

11. Invasion 11 Refers to entry of bacteria into host cells, leading to spread within the host tissues. Highly invasive pathogens produce spreading or generalized lesions, while less invasive pathogens cause localized lesions.

12. Invasion (Cont..) 12 Important virulence factors that help in invasion include: Virulence marker antigen or invasion plasmid antigens in Shigella Enzymes: Invasion of bacteria is enhanced by many enzymes such as: hyaluronidase, collagenase, streptokinase , IgA proteases.

13. Invasion (Cont..) 13 Antiphagocytic Factors : Bacteria are rapidly killed once they are ingested by phagocytes. Some pathogens develop strategies to evade phagocytosis by several antiphagocytic factors, the most important ones being – Capsule Cell wall proteins Cytotoxins

14. Intracellular Survival 14 Mechanism of intracellular survival Organism Inhibition of phagolysosome fusion Legionella species Mycobacterium tuberculosis Chlamydia species Resistance to lysosomal enzymes Salmonella Typhimurium Coxiella species Mycobacterium leprae Adaptation to cytoplasmic replication Listeria , Rickettsia Francisella tularensis

15. Intracellular Survival (Cont..) 15 Facultative intracellular bacteria Obligate intracellular Salmonella Typhi , Brucella Mycobacterium leprae Legionella, Listeria, Nocardia Rickettsia Neisseria meningitidis , Yersinia Chlamydia Mycobacterium tuberculosis Coxiella burnetii

16. Toxins 16 Endotoxins They are the lipid A portion of lipopolysaccharide. They are present as an integral part of the cell wall of Gram negative bacteria. They are released from the bacterial surface by natural lysis of the bacteria and are responsible for various biological effects in the host.

17. Toxins (Cont..) 17 Effects of bacterial endotoxins

18. Toxins (Cont..) 18 Biological effects of endotoxins: Macrophage activation Complement activation Endothelial activation Coagulation pathways activation Platelet activation Mast cell activation In Gram negative septicemia

19. Toxins (Cont..) 19 Exotoxins Heat labile proteins; secreted by certain species of both gram-positive and gram-negative bacteria and diffuse readily into the surrounding medium. High potency Used for vaccine Specific action

20. Bacterial exotoxins and their mechanism of action 20 Organisms Toxins (Exotoxins) Mechanism Staphylococcus aureus Enterotoxin, Toxic shock syndrome toxin Act as super antigen; stimulate T cell non-specifically, to release of large amounts of cytokines. Streptococcus pyogenes Streptococcal pyrogenic exotoxin Corynebacterium diphtheriae Diphtheria toxin (DT) Inhibits protein synthesis (by inhibiting elongation factor-2) Bacillus anthracis Anthrax toxin ↑ cAMP in target cell, edema Clostridium perfringens α toxin and other major and minor toxins Lecithinase and phospholipase activity → causes myonecrosis Clostridium tetani Tetanus toxin ( tetanospasmin ) Decrease in neurotransmitter (GABA and glycine) release from the inhibitory neurons → spastic paralysis

21. Bacterial exotoxins and their mechanism of action (Cont..) 21 Organisms Toxins (Exotoxins) Mechanism Clostridium botulinum Botulinum toxin Decrease in neurotransmitter (acetyl choline) release from neurons → flaccid paralysis Escherichia coli ( diarrheagenic ) Heat labile toxin (LT) Activation of adenylate cyclase → ↑ cAMP in target cell → secretory diarrhea Heat stable toxin (ST) ↑cGMP in target cell → secretory diarrhea Verocytotoxin Inhibit protein synthesis (by inhibiting ribosome) Shigella dysenteriae type-1 Shiga toxin Vibrio cholerae Cholera toxin (CT) Activation of adenylate cyclase → ↑ cAMP in target cell → secretory diarrhea Pseudomonas Exotoxin-A Inhibit protein synthesis (by inhibiting elongation factor-2)

22. Differences between bacterial endotoxins and exotoxins 22 Feature Endotoxins Exotoxins Nature Lipopolysaccharides Proteins Source Part of cell wall of Gram negative bacteria Secreted both by Gram positive & negative bacteria; diffuse into surrounding medium Released by Cell lysis , Not by secretion Actively secreted by the bacteria Heat stability Highly stable Heat labile destroyed at 60 o C Mode of action ↑IL-1 and TNF Mostly enzyme like action

23. Differences between bacterial endotoxins and exotoxins (Cont..) 23 Feature Endotoxins Exotoxins Effect Non-specific (fever, shock, etc) Specific action on particular tissues Tissue affinity No Specific affinity for tissues Fatal dose Only large doses are fatal More potent, even smaller doses- fatal Antigenicity Poorly antigenic   Highly antigenic Neutralisation by antibodies Ineffective Neutralized by specific antibodies Used for vaccine No effective vaccine is available using endotoxin Toxoid forms are used as vaccine; e.g. tetanus toxoid