Mechanisms Of Pathogenicity

Mechanisms of Pathogenicity How do microorganisms cause ?disease

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Pathogenicity The ability to cause disease in a host virulence Is the degree of Pathogenicity LD50 lethal dose to kill 50% of inoculated hosts ID50 infectious dose number of microorganisms needed to cause disease in 50% of the test population

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predisposing factors  make the body more susceptible  alter the course of a disease  Gender  Nutritional status  Weather and climate  Fatigue  Age  Habits  Life style  Pre-existing illness  Emotional disturbance  Chemotherapy 27/11/09

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Characteristics for successful pathogen Transmissible Adherence to host cells Invasion of host cell and tissues Ability to multiply Ability to avoid host defense mechanisms Ability to damage host tissues

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Transmission of infections  droplet contact – coughing, sneezing  direct physical contact - touch, sexual contact  indirect contact - soil contamination, contaminated surface  airborne transmission - microorganism remains in the air for long periods  fecal-oral transmission - contaminated food, water sources  vector borne transmission - carried by insects or other animals

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Virulence Factors  Adherence to host cells  via surface projections called adhesions, colonization factors, or ligands  Fimbriae  E. coli has ligands on which attach it to intestinal epithelial cell  afimbrial in nature  Streptococcus mutans tooth enamel via an extracellular polysaccharide  pili  Neisseria gonorrhoeae attach it to epithelial cells in the genitourinary tract.  Protein A in Staphylococcus aureus  Protein M and via lipoteichoic acids  Streptococcus pyogenes bind to fibronectin on the surface of epithelial cells

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Bacterial adhesions may be fimbrial or afimbrial in nature

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Adhesions

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PENETRATE HOST DEFENSE  Factors resist host immune defense  Antiphagocytic Factors  Capsules and M protein  interfere with the ability of phagocytic cells  IgA protease  cleave IgA found at mucosal surfaces attachment  flagella  allow bacteria to swim away from phagocytic cells

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Action of Protein A

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Enzymatic Virulence Factors  PENETRATION AND SPREAD  Coagluase (Staphylococcus aureus)  fibrin clot to wall the organism off and protect it from host defenses  lipases  that break down lipids  Streptokinase (Streptococcus pyogenes)  Hyaluronidase (Many pathogens)  dissolves hyaluronic acid which holds cells together 27/11/09

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Enzymatic Virulence Factors Collagenase (Many pathogens) break down collagen which forms the framework of muscles Leucocidin (Many pathogens) that kill WBCs Hemolysin (Many pathogens) destroy RBCs as well as other types of tissue cells to allow dissemination

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Enzymes Cont.  Lecithinase degrade lecithin of connective tissues  IgA1 Protease (N. gonorrhoeae) Split IgA and inactivate its activity  Streptolysin O Lysis RBC

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Damaging host cells  Direct damage  Attachment, penetration and multiplication  Toxins  can also cause direct damage  What is a toxin?  are poisonous substances  responsible for the Pathogenicity of the microbe  Toxemia refers to symptoms caused by toxins in the blood  toxigenicity 27/11/09

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types of toxins  Exotoxins and Endotoxins  Exotoxins  Properties of exotoxins  produced by either gram-positive or gram-negative bacteria  Is secreted by the bacteria  Most exotoxins are peptide or protein  genes are carried on plasmids or encoded in lysogenic bacteriophages  soluble in body fluids and are transported rapidly throughout the body

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Exotoxins cont.  Are among the most lethal toxins known to man  Are disease specific  The host can produce anti-toxins (antibodies)  Can be inactivated to produce toxoids  stimulate the body to produce protective anti-toxin antibodies (vaccinations)  Most exotoxins are heat sensitive (exception: enterotoxin of Staphylococcus aureus)  Classes of exotoxins  Neurotoxins  Interfere with proper synaptic transmissions in neurons

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Classes of exotoxins  Cytotoxins Inhibit specific cellular activities, such as protein synthesis  Enterotoxins Interfere with water reabsorption in the large intestine  irritate the lining of the gastrointestinal tract

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Many have an A (toxic effect)/B (binding) structure

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Botulinum toxin  Clostridium botulinum not released until the death of the microorganism acts at the neuromuscular junction prevent the transmission of nerve impulses leading to flaccid paralysis death from respiratory failure

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Botulinum Toxin Flaccid Paralysis

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Tetanus toxin  produced by Clostridium tetani  causes excitation of the CNS  leading to spasmodic contractions  death from respiratory failure  is also called “lockjaw disease Diphtheria toxin  produced by Corynebacterium diphtheriae  inhibits protein synthesis in eukaryotic cells  cause death.

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Tetanus toxin spastic paralysis

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Diphtheria toxin

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Staphylococcal enterotoxin  produced by Staphylococcus aureus  induces vomiting and diarrhea  by preventing the absorption of water in the intestine Vibrio enterotoxin  produced by Vibrio cholera  alters the water and electrolyte balance in the intestine  leading to a very severe life threatening, watery diarrhea.

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Vibrio enterotoxin

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Endotoxins  Produced only by gram-negative bacteria  are a component of the gram-negative cell wall  requires the presence of the bacteria in the host  may be released from the cell wall as the cells die and disintegrate  composed of Lipid A  Only large doses are lethal  Mode of action  All produce the same signs and symptoms  STIMULATE RELEASE OF CYTOKINES  ALTERNATIVE PATHWAY 27/11/09

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Mode of action  CAUSE SEPTIC SHOCK, GRAM (-) SEPSIS  HYPOTENSION  FEVER (pyrogenic response) (  MASSIVE ORGAN FAILURE  HARD TO REVERSE  Irritation/inflammation of epithelium, GI irritation,  capillary/blood vessel inflammation  hemorrhaging

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Endotoxin and the pyrogenic response

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Endotoxin versus exotoxin

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Endotoxin versus exotoxin

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Summary of mechanisms of Pathogenicity

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