Microbial pathogenicity; Toxin, Cell, Protein

Microbial pathogenicity depends upon the sum total of several factors as described below.
Microbial pathogenicity depends upon the sum total of several factors as described below.


1. Route of transmission of infection 
2. Infective dose of the organism: Minimum inoculum size that is capable of initiating an infection. (table given below)

Low infective dose
Large infective dose
Shigella: Very low (as low as 10 bacilli)
Escherichia coli  (106 – 108 bacilli)
Cryptosporidium parvum: very low (10 to 30 oocysts)
Salmonella (102 – 105  bacilli)
Escherichia coli O157: H7  (< 10 bacilli)
Vibrio cholerae (106 – 108 bacilli)
Entamoeba and Giardia: few cysts

Campylobacter jejuni (500 bacilli)


3. Evasion of the local defenses
4. Adhesion: By Fimbriae or pili, other adhesins, biofilm formation
5. Invasion: 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: Hyaluronidase, Collagenase, Streptokinase (fibrinolysin) and IgA proteases
  • Antiphagocytic factors: Capsule
  • Cell wall protein such as: Protein A of Staphylococcus aureus and M protein of Streptococcus pyogenes
  • Cytotoxins: Interfere with chemotaxis or killing of phagocytes. For example, S. aureus produces hemolysins and leukocidins that lyse and damage RBCs and WBCs.
Mechanism of intracellular survival
Organism
Inhibition of  phagolysosome fusion
Legionella species, Mycobacterium tuberculosis, Chlamydia
Resistance to lysosomal enzymes
Salmonella Typhimurium, Coxiella, Mycobacterium leprae, Leishmania
Adaptation to cytoplasmic replication
Listeria, Rickettsia and Francisella tularensis

Examples of Obligate intracellular organism include:

  • Bacteria: Mycobacterium leprae, Rickettsia, Chlamydia and Coxiella
  • All viruses
  • Fungi: Pneumocystis jirovecii
  • Parasite: Toxoplasma, Cryptosporidium, Plasmodium, Leishmania, Babesia, Trypanosomacruzi

Differences between bacterial endotoxins and exotoxins

Endotoxins
Exotoxins
Lipopolysaccharides in nature
Protein in nature
Part of Gram-negative bacterial cell wall
Secreted both by Gram-positive and negative bacteria; diffuse into surrounding medium
Released by cell lysis, Not by secretion
Actively secreted by the bacteria
Highly stable
Heat labile destroyed at 60°C
Mode of action – Induces ↑IL-1 and TNF
Mostly enzyme like action
Nonspecific (fever, shock, etc.)
Specific action on particular tissues
No specific affinity for tissues
Specific affinity for tissues
Only large doses are fatal
More potent, even smaller doses fatal
Poorly antigenic
Highly antigenic
Neutralization by antibodies is ineffective
Neutralized by specific antibodies
No effective vaccine is available using endotoxin
Toxoid forms are used as vaccine, e.g. tetanus toxoid

Exotoxins and their mechanisms of action

Toxins (Exotoxins)
Mechanism
Enterotoxin and TSST of S.aureus
Streptococcal pyrogenic exotoxin
Act as super antigen; stimulate T cell non-specifically, to release of large amounts of cytokines.
Diphtheria toxin and Exotoxin-A of Pseudomonas
Inhibits protein synthesis (by inhibiting elongation factor-2)
Anthrax toxin
↑cAMP in target cell, edema
α toxin  of Clostridium perfringens
Lecithinase and phospholipase activity → causes myonecrosis
Tetanus toxin (tetanospasmin)
Decrease in neurotransmitter (GABA and glycine) release from the inhibitory neurons → Spastic paralysis
Botulinum toxin
Decrease in neurotransmitter (acetyl choline) release from neurons → Flaccid paralysis
Heat labile toxin of ETEC and Cholera toxin (V.cholerae)
Activation of adenylate cyclase → ↑cAMP in target cell → Secretory diarrhea
Heat stable toxin Verocytotoxin (EHEC) and  Shiga toxin (Shigella dysenteriae type-1)
↑cGMP in target cell → Secretory diarrhea
Diphtheria toxin and Exo toxin -A of Pseudomonas
Inhibit protein  synthesis (by inhibiting ribosome)

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