Chapter 15 Microbial Mechanisms of Pathogenicity

Chapter 15 – Microbial Mechanisms of

Pathogenicity

Mechanisms of Pathogenicity

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pathogenicity: the ability to cause disease by overcoming a host defenses.

Virulence: the extent of pathogenicity.

How Microorganisms Enter A Host

1. Portals of Entry

  • Mucous membranes

    • Example: Conjunctiva (mucus membrane the lines the eyelids)

  • Skin

  • The Parental route (injured or penetrated barrier such as skin)

2. Portal of Entry Preferential

  • Many pathogens have a preferred portal of entry as a requirement before they can cause a disease otherwise they are ineffective.

  • For example: Salmonella typhi must be swallowed before it can cause typhoid fever.

  • Another example: Strepococci must be inhaled to cause pneumonia

3. Numbers of Invading Microbes

  • The more microbes, the more they are likely to overcome the body’s defenses.

  • ID50

    • Infections dose for 50% of a sample population.

    • It is an expression of the virulence of a microbe

  • LD50

    • Lethal dose for 50% of a sample population

    • It is an expression of the potency of a toxin.

4. Adherence

  • Most pathogens must attach to host cells to be pathogenic.

  • The adhesions or ligands on the surface molecules of the pathogen bind on the complementary receptors of the host cells.

  • Biofilms are masses of microbes and their cellular products that attach to living and nonliving surfaces that share available nutrients.

How Bacterial Pathogens Penetrate Host Defenses

1. Capsules

  • Some bacteria have glycocalyx (sugary coat) that form capsule that increases their virulence and avoid phagocytosis.

  • Streptococcus pneumoniae (causative agent of pneumococcal pneumonia)

  • Bacillus anthracis (cause of anthrax) escapes phagocytosis of its capsule.

2. Cell Wall Components

  • Certain pathogens have chemical substances such as acids and proteins that contribute to their virulence

  • Mycobacterium tuberculosis have mycolic acid or waxy lipid that make up their cell wall to avoid phagocytosis.

  • Streptococcus pyogens have M protein on their surface and fimbrai to resist phagocytosis

  • Neisseria gonorrhoeae use fimbria and Opa protein on their outer membrane that the host cells take in and then grow inside.

3. Enzymes

  • Exoenzyme (extracellular enzymes) aids in the virulence of some bacteria.

  • Coagulases clot the fibrinogen in blood isolating and protecting the bacterium from phagocytosis and other defense mechanisms of the host.

    • Some members of genus Staphylococcus

  • Kinases digest clots to prevent infection isolation formed by the host.

    • Streptococcus pyogenes

    • Staphylococcus auereus

  • Hyaluronidase produces hyaluronic (connective tissue) acid that cause blackening of infected wounds and help spread the infection.

    • Certain streptococci

    • Some clostridia

  • Collagenase break down collagen to spread gas gangrene

    • Several species of Clostridium

  • IgA proteases produce by pathogens destroy antibodies IgA produce by host

    • Neisseria gonorrheae

    • N. meningitidis

4. Antigenic Variation

  • Some pathogens change their surface antigens before antibodies get to them.

  • Examples includes: N. gonorrhea (cause gonorrhea), Influenzavirus (cause flu), Trypanosoma brucei gambiense (cause African sleeping sickness)

How Bacterial Pathogens Damage Host Cells

1. Using the Host’s Nutrients: Siderophores

  • Siderophores are proteins released by pathogenic bacteria to take iron away from iron-transport proteins (ferritin, transferring, lactoferrin) necessary for their growth by forming iron-siderophore complex.

2. Direct Damage

  • The pathogens when attached used the host cells for nutrients, grow inside, produce waste products and rupture the host cells.

  • Examples: N. gonorrhoeae, E. coli, Shigella, Salmonella.

3. The Production of Toxins

  • Toxins are poisonous substances produced by certain microorganisms

  • Toxigenicity is the capacity of microorganisms to produce toxins.

  • Toxemia is refers to the presence of toxins in the blood.

  • Exotoxins are proteins and enzymes produced mostly inside gram positive bacteria and some negative bacteria and then released in the surrounding medium to destroying specific parts of the host’s cells or inhibit certain metabolic functions.

    • Botulinum (1 mg can kill 1 million)

  • Antitoxins refers to antibodies that provide immunity to exotoxins

  • Toxoids refers to altered exotoxins that no longer cause disease because they are inactivated by heat or formaldehyde, iodine, or other chemicals but can still produce antitoxins.

  • Endotoxins are produced on the cell wall of gram negative bacteria and produce the same signs and symptoms regardless of the species of microorganism but not to the same degree.

Exotoxin Properties

Bacterial source

  • Mostly from gram positive bacteria. Few are gram negative

Relation to microorganism

  • Metabolic product of growing cell

Chemistry

  • Proteins

Pharmacology (effect on body)

  • Specific for a particular cell structure or function in the host (affects cell functions, nerves, GI tract)

Heat Stability

  • Unstable; can be destroyed at 60-80 deg Cel

Toxicity (ability to cause disease)

  • High

Fever-producing

  • No

Immunology (relation to antibodies)

  • Can be converted to toxoid to immunize against toxin; neutralized by antitoxin

Lethal does

  • Small

Representative disease

  • Gas gangrene, tetanus, botulism, diptheria, scarlet fever

Diseases Caused by Exotoxins

1. Staphylococcus Aureus

  • Scalded skin syndrome: One exotoxin causes skin to separate and slough off.

  • Food poisoning: Enterotoxin causes secretion of fluids and electrolytes resulting and diarrhea.

  • Toxic shock syndrome: Toxin causes secretions of fluids and electrolytes from capillaries that decreases blood volume and pressure.

2. Clostridium botulinum (gram +)

  • Botulism: Neutrotoxin prevents that transmission of nerve impulses resulting in flaccid paralysis.

3. Clostridium tetani

  • Tetanus: Neutrotoxin blocks nerve impulse to muscle relaxation pathway resulting in uncontrollable muscle contraction.

4. Clostridium difficile

  • Antibiotic-associated diarrhea: Enterotoxin causes secretion of fluids and electrolytes resulting in diarrhea. Cytotoxin disrupts host cytoskeleton.

5. Clostridium perfringens and other Clostridiums

  • Gas gangrene and food poisoning: One exotoxin (cytotoxin) causes hemolysis. Another exotoxin (enterotoxin) related to food poisoning causes and causes diarrhea.

6. Streptococcus pyogens

  • Scarlet fever: cytoxin inhibit cells in circulatory system producing rash and fever.

7. Corynebacterium diphtheriae

  • Diphtheria: general cytoxin infection inhibiting protein synthesis especially nerve, heart and kidney cells.

8. Vibrio Cholorae

  • Cholera: Enterotoxin causes secretion of large amounts of fluids and electrolytes resulting in diarrhea.

9. Enterotoxigenic Escherichia coli and Shigella spp

  • Traveler’s diarrhea: Enterotoxin causes secretion of large amounts of fluids and electrolytes resulting in diarrhea.

Endotoxin Properties

Bacterial source

  • Only gram negative

Relation to microorganism

  • Present in LPS (lipopolysaccharide) of outer membrane of cell wall and released with destruction of cell or during cell division.

Chemistry

  • Lipid portion of LPS of outer membrane

Pharmacology (effect on body)

  • General such as fever, weakneses, aches, and shock; all produce the same effects

Heat Stability

  • Stable; can withstand autoclaving (121 deg for 1 hour)

Toxicity (ability to cause disease)

  • Low

Fever-producing

  • Yes

Immunology (relation to antibodies)

  • Not easily neutralized by antitoxin; effective toxoids cannot be made to immunize against toxin

Lethal does

  • Considerably larger

Representative disease

  • Typhoid fever, UTI (urinary tract infection), and meningococcal meningitis

Pathogenic Properties of Viruses

Cytopathic Effects of Viruses

  • Cytopathic effects (CPE) is the visible effects of viral infection.

  • Cytocidal effects are those CPE that result in cell death.

  • Noncytocidal effects are those that result in cell damage.

  • Interferons are antiviral proteins produce by some virus-infected cells to protect neighboring uninfected cells from viral infection.

Pathogenic Properties of Helminths

  • Some of these organisms use the host’s tissue for nutrients to grow or produce large parasitic masses.

Portal of Exit

  • Generally the same as portal of entry for specific organism.

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