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

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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 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

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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

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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

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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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